Goals: We conducted a systematic review and network meta-analysis to investigate the effect of endoscopic ultrasound-guided celiac plexus neurolysis added to medical management (EUS-CPN+MM) compared with MM, percutaneous CPN (P-CPN)+MM, or intraoperative CPN (I-CPN)+MM for abdominal pain associated with unresectable pancreatic cancer., Background: Many approaches to CPN have been proposed since 1919. EUS-CPN, which is less invasive and safer than traditional procedures, has been preferred recently, but the superiority of EUS-CPN+MM has not been fully investigated., Study: We performed searches of PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on March 16, 2021. We conducted the network meta-analysis using a frequentist weighted least-squares approach. We used a random-effects model to synthesize the primary outcome, defined as the mean difference between treatment groups in standardized pain intensity scores at 4 and 12 weeks., Results: We selected 10 RCTs involving 662 individuals. At 4 weeks, the estimated mean difference between the EUS-CPN+MM and MM groups was -1.30 (95% CI: -2.19 to -0.41) in favor of EUS-CPN+MM, and that between the EUS-CPN+MM and P-CPN+MM groups was -0.88 (95% CI: -1.82 to 0.06). At 12 weeks, the estimated mean difference between the EUS-CPN+MM and MM groups was -2.58 (95% CI: -3.68 to -1.48), and that between the EUS-CPN+MM and P-CPN+MM groups was -2.44 (95% CI: -4.03 to -0.84), both in favor of EUS-CPN+MM., Conclusions: The combination of EUS-CPN+MM was effective at 4 and 12 weeks, although the risk of bias in synthesized studies was generally high, necessitating careful interpretation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)