BackgroundThere are increasing concerns regarding the abusive potential of gabapentinoids putting at risk patients with neuropathic pain requiring long-term pain management. The evidence to support this is rather inconcusive.AimThis systematic review aimed to evaluate the safety and efficacy of gabapentinoids in the management of neuropathic pain with a focus on randomised controlled trials (RCTs) and categorising the side effects according to the body systems they were affecting.MethodSearches were conducted in MEDLINE (PubMed), EMBASE, Web of Science, PsycoINFO, and CINAHL (EBSCO), and included RCTs to identify and critically appraise studies investigating safety and therapeutic effects of gabapentionoids in adults with neuropathic pain. Data extraction was conducted using an established Cochrane form and the risk-of-bias tool was used in the assessment of quality.Results50 studies (12,398 participants) were included. The majority of adverse events pertained to the nervous system (7 effects) or psychiatric (3 effects) disorders. There were more adverse effects reported with pregabalin (36 effects) than with gabapentin (22 effects). Six pregabalin studies reported euphoria as a side effect, while no studies reported euphoria with gabapentin. This was the only side effect that may correlate with addictive potential. Gabapentioids were reported to significantly reduce pain compared to placebo.ConclusionDespite RCTs documenting the adverse events of gabapentionoids on the nervous system, there was no evidence of gabapentinoid use leading to addiction, suggesting an urgent need to design studies investigating their abusive potential.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11096-022-01528-y.