Background. The role of amitriptyline in musculoskeletal pain is not as clearly defined as in classical neuropathic pain conditions. Objective. To assess the efficacy and effectiveness of amitriptyline in the treatment of pain in musculoskeletal complaints. Methods. An extensive search (including Medline, Embase and Web of Science) was made up to April 2016 for randomised controlled trials on amitriptyline in musculoskeletal complaints compared to placebo, usual care, or other analgesic use. Included studies were assessed for risk of bias. Outcomes of interest were pain reduction and function improvement. Results. Of the 2066 articles identified, seven were finally included. These studies were performed in patients with low back pain (4), rheumatoid arthritis (2), and patients with arm pain from repetitive use (1). No meta-analysis was performed due to clinical heterogeneity of the studies. Two studies with low risk of bias found positive results. One study found that 50 mg/day of amitriptyline [Visual Analogue Scale (VAS)-3.9 points] resulted in a significantly greater reduction in pain than treatment with pregabalin 600 mg/day (VAS-2.9 points) and improved function (improvement on the Oswestry Disability Index >20%: 65% versus 49.5%). Amitriptyline improved function in arm pain compared to placebo (Upper Extremity Function Scale:-3.9 versus 0.8). A similar amount of side-effects occurred in the amitriptyline and the comparison groups. Conclusion. Few studies have evaluated the use of amitriptyline in musculoskeletal complaints. Although amitriptyline may be effective in musculoskeletal complaints, more studies are required to establish for whom amitriptyline works better than other analgesics.