Individuals with an extremity amputation are predisposed to persistent pain that reduces their quality of life. Residual limb pain is defined as pain that is felt in the limb after amputation. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of 5 databases from inception to June 2020 was performed and is registered under the PROSPERO ID: CRD42020199297. Included studies were clinical trials with residual limb pain assessed at a minimum follow-up of 1 week. Meta-analyses of residual limb pain prevalence and severity were performed with subgroups of extremity and amputation etiology. Twenty clinical trials met criteria and reported on a total of 1347 patients. Mean patient ages ranged from 38 to 77. Residual limb pain prevalence at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years, respectively, was 50%, 11%, 23%, 27%, 22%, and 24%. Mean residual limb pain severity at the 6 months or longer follow-up was 4.19 out of 10 for cancer amputations, 2.70 for traumatic amputations, 0.47 for vasculopathy amputations, 1.01 for lower extremity amputations, and 3.56 for upper extremity amputations. Residual limb pain severity varies according to the etiology of amputation and is more common after upper extremity amputation than lower extremity amputations. The most severe pain is reported by patients undergoing amputations due to cancer, followed by traumatic amputations, while vascular amputation patients report lower pain severity. Promising methods of reducing long-term pain are preoperative pain control, nerve or epidural blocks, use of memantine, calcitonin-containing blocks, and prophylactic nerve coaptations.