Objective: To investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for relief of pain in adults., Design: Systematic review and meta-analysis., Data Sources: Medline, Cochrane Central, Embase (and others) from inception to July 2019 and updated on 17 May 2020., Eligibility Criteria for Study Selection: Randomised controlled trials (RCTs) comparing strong non-painful TENS at or close to the site of pain versus placebo or other treatments in adults with pain, irrespective of diagnosis., Data Extraction and Synthesis: Reviewers independently screened, extracted data and assessed risk of bias (RoB, Cochrane tool) and certainty of evidence (Grading and Recommendations, Assessment, Development and Evaluation). Mean pain intensity and proportions of participants achieving reductions of pain intensity (≥30% or > 50%) during or immediately after TENS. Random effect models were used to calculate standardised mean differences (SMD) and risk ratios. Subgroup analyses were related to trial methodology and characteristics of pain., Results: The review included 381 RCTs (24 532 participants). Pain intensity was lower during or immediately after TENS compared with placebo (91 RCTs, 92 samples, n=4841, SMD=-0·96 (95% CI -1·14 to -0·78), moderate-certainty evidence). Methodological (eg, RoB, sample size) and pain characteristics (eg, acute vs chronic, diagnosis) did not modify the effect. Pain intensity was lower during or immediately after TENS compared with pharmacological and non-pharmacological treatments used as part of standard of care (61 RCTs, 61 samples, n=3155, SMD = -0·72 (95% CI -0·95 to -0·50], low-certainty evidence). Levels of evidence were downgraded because of small-sized trials contributing to imprecision in magnitude estimates. Data were limited for other outcomes including adverse events which were poorly reported, generally mild and not different to comparators., Conclusion: There was moderate-certainty evidence that pain intensity is lower during or immediately after TENS compared with placebo and without serious adverse events., Prospero Registration Number: CRD42019125054., Competing Interests: Competing interests: MIJ (taken from ICMJE form); MIJ reports grants from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from TENSCare, other from Actegy Ltd, other from LifeCare Ltd, other from Eurocept Pharmaceuticals, personal fees from Oxford University Press, outside the submitted work. MIJ was involved in conducting the following studies that were considered for inclusion in the work submitted for publication. (1) Dissanayaka TD, Pallegama RW, Suraweera HJ, Johnson MI, Kariyawasam AP. (2016). Comparison of the Effectiveness of Transcutaneous Electrical Nerve Stimulation and Interferential Therapy on the Upper Trapezius in Myofascial Pain Syndrome: A Randomized Controlled Study. American Journal of Physical Medicine and Rehabilitation 2016 Sep;95(9):663-72. (2) Palmer S, Domaille M, Cramp F, Walsh N, Pollock J, Kirwan J, Johnson MI. (2014) Transcutaneous Electrical Nerve Stimulation as an adjunct to education and exercise for knee osteoarthritis: a randomised controlled trial. Arthritis Care & Research 2014: 66(3), 387–394 – Funded by the Physiotherapy Research Foundation (part of the Chartered Society of Physiotherapy Charitable Trust) and Above & Beyond Charities. (3) Pallett EJ, Rentowl P. Johnson MI, Watson PJ (2014) Implementation fidelity of self-administered Transcutaneous Electrical Nerve Stimulation (TENS) in patients with chronic back pain: An observational study. Clin J Pain. 2014: Mar;30(3):224-31. (4) Kolen AF, de Nijs RN, Wagemakers FM, Meier AJ, Johnson MI (2012) The effects of spatially targeted transcutaneous electrical nerve stimulation (TENS) using an electrode array that measures skin resistance on pain and mobility in patients with osteoarthritis in the knee: A randomized controlled trial. Pain. 2012 Feb;153(2):373-81 - Funded by Phillips Research Europe., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)