OBJECTIVES: To conduct a systematic review and comparison of pharmacologic therapies for treating neuropathic pain (NeP) associated with stroke, HIV, trauma, and multiple sclerosis (MS). METHODS: Systematic searches of electronic literature databases were conducted to identify randomized, blinded, controlled trials of NeP associated with stroke, HIV, trauma, and MS published through June 2011. Identified references were screened for inclusion by two independent reviewers. Data extracted and evaluated from each study included pain severity (11-point numeric rating scale [NRS] or visual analog scale [VAS]), proportion of patients achieving 30% and 50% reductions in pain, adverse events (AEs), and discontinuations. RESULTS: Eighteen studies met inclusion/exclusion criteria. Sample sizes were generally small (11-145 patients) except for 2 HIV, 1 trauma, and 1 post-stroke pain containing 219-307 patients. Two of the four stroke studies presenting mean treatment effects over that of placebo reported reductions of -0.2 to -0.3 on NRS for pregabalin, amitriptyline and carbamazepine. Of the nine HIV studies, topical capsaicin gave the largest treatment effect on the NRS (-2.5). NGX-4010 was the only treatment showing higher relative benefit for 30% or 50% pain reduction compared with placebo. Of three trauma studies, pregabalin, mexiletine, and gabapentin showed NRS or VAS mean pain reductions numerically superior to placebo, although some effects were very small. Only pregabalin provided a significant relative benefit of 30% pain reduction. Two MS studies (<30 patients each) showed mixed efficacy for lamotrigine (+0.8 NRS) and levetiracetam (-33.1 VAS). Most studies had insufficient data to compare AE risk. Available discontinuation data showed similar rates between treatments and placebo. CONCLUSIONS: Studies of NeP treatment associated with stroke, HIV, trauma, and MS were few, frequently small, and lacked measurements of uncertainty necessary to perform adequate comparisons. More and better evaluation of NeP treatment in patients with these conditions are needed.