Background: Peripherally inserted central catheters (PICCs) facilitate diagnostic and therapeutic interventions in health care. PICCs can fail due to infective and non-infective complications, which PICC materials and design may contribute to, leading to negative sequelae for patients and healthcare systems., Objectives: To assess the effectiveness of PICC material and design in reducing catheter failure and complications., Search Methods: The University of Queensland and Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the WHO ICTRP and ClinicalTrials.gov trials registers to 16 May 2023. We aimed to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, as well as relevant systematic reviews, meta-analyses, and health technology assessment reports. We contacted experts in the field to ascertain additional relevant information., Selection Criteria: We included randomised controlled trials (RCTs) evaluating PICC design and materials., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were venous thromboembolism (VTE), PICC-associated bloodstream infection (BSI), occlusion, and all-cause mortality. Secondary outcomes were catheter failure, PICC-related BSI, catheter breakage, PICC dwell time, and safety endpoints. We assessed the certainty of evidence using GRADE., Main Results: We included 12 RCTs involving approximately 2913 participants (one multi-arm study). All studies except one had a high risk of bias in one or more risk of bias domain. Integrated valve technology compared to no valve technology for peripherally inserted central catheter design Integrated valve technology may make little or no difference to VTE risk when compared with PICCs with no valve (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.19 to 2.63; I² = 0%; 3 studies; 437 participants; low certainty evidence). We are uncertain whether integrated valve technology reduces PICC-associated BSI risk, as the certainty of the evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Integrated valve technology may make little or no difference to occlusion risk when compared with PICCs with no valve (RR 0.86, 95% CI 0.53 to 1.38; I² = 0%; 5 studies; 900 participants; low certainty evidence). We are uncertain whether use of integrated valve technology reduces all-cause mortality risk, as the certainty of evidence is very low (RR 0.85, 95% CI 0.44 to 1.64; I² = 0%; 2 studies; 473 participants). Integrated valve technology may make little or no difference to catheter failure risk when compared with PICCs with no valve (RR 0.80, 95% CI 0.62 to 1.03; I² = 0%; 4 studies; 720 participants; low certainty evidence). We are uncertain whether integrated-valve technology reduces PICC-related BSI risk (RR 0.51, 95% CI 0.19 to 1.32; I² = not applicable; 2 studies (no events in 1 study); 542 participants) or catheter breakage, as the certainty of evidence is very low (RR 1.05, 95% CI 0.22 to 5.06; I² = 20%; 4 studies; 799 participants). Anti-thrombogenic surface modification compared to no anti-thrombogenic surface modification for peripherally inserted central catheter design We are uncertain whether use of anti-thrombogenic surface modified catheters reduces risk of VTE (RR 0.67, 95% CI 0.13 to 3.54; I² = 15%; 2 studies; 257 participants) or PICC-associated BSI, as the certainty of evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces occlusion (RR 0.69, 95% CI 0.04 to 11.22; I² = 70%; 2 studies; 257 participants) or all-cause mortality risk, as the certainty of evidence is very low (RR 0.49, 95% CI 0.05 to 5.26; I² = not applicable; 1 study; 111 participants). Use of anti-thrombogenic surface modified catheters may make little or no difference to risk of catheter failure (RR 0.76, 95% CI 0.37 to 1.54; I² = 46%; 2 studies; 257 participants; low certainty evidence). No PICC-related BSIs were reported in one study (111 participants). As such, we are uncertain whether use of anti-thrombogenic surface modified catheters reduces PICC-related BSI risk (RR not estimable; I² = not applicable; very low certainty evidence). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces the risk of catheter breakage, as the certainty of evidence is very low (RR 0.15, 95% CI 0.01 to 2.79; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Antimicrobial impregnation compared to non-antimicrobial impregnation for peripherally inserted central catheter design We are uncertain whether use of antimicrobial-impregnated catheters reduces VTE risk (RR 0.54, 95% CI 0.05 to 5.88; I² = not applicable; 1 study; 167 participants) or PICC-associated BSI risk, as the certainty of evidence is very low (RR 2.17, 95% CI 0.20 to 23.53; I² = not applicable; 1 study; 167 participants). Antimicrobial-impregnated catheters probably make little or no difference to occlusion risk (RR 1.00, 95% CI 0.57 to 1.74; I² = 0%; 2 studies; 1025 participants; moderate certainty evidence) or all-cause mortality (RR 1.12, 95% CI 0.71 to 1.75; I² = 0%; 2 studies; 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter failure (RR 1.04, 95% CI 0.82 to 1.30; I² = not applicable; 1 study; 221 participants; low certainty evidence). Antimicrobial-impregnated catheters probably make little or no difference to PICC-related BSI risk (RR 1.05, 95% CI 0.71 to 1.55; I² = not applicable; 2 studies (no events in 1 study); 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter breakage (RR 0.86, 95% CI 0.19 to 3.83; I² = not applicable; 1 study; 804 participants; low certainty evidence)., Authors' Conclusions: There is limited high-quality RCT evidence available to inform clinician decision-making for PICC materials and design. Limitations of the current evidence include small sample sizes, infrequent events, and risk of bias. There may be little to no difference in the risk of VTE, PICC-associated BSI, occlusion, or mortality across PICC materials and designs. Further rigorous RCTs are needed to reduce uncertainty., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)