Background: Alcohol use disorders (AUD) involving hazardous, harmful, and addictive misuse of alcohol are widespread in most parts of the world. The aim of this study was to review the effect of disulfiram in the treatment of patients with AUD. The effect of disulfiram was evaluated according to the primary outcome of an intake of alcohol below 30 and 20 g/d for men and women, respectively, as well as secondary outcomes such as days until relapse, alcohol intake, and numbers of drinking days. Methods: A systematic review of the literature was conducted using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Results: Eleven randomized controlled trials were included with a total of 1,527 patients. They compared disulfiram treatment with placebo, none or other abstinence-supportive treatments. Overall, 6 studies reported of a significant better effect on abstinence for patients treated with disulfiram. Six of 9 studies measuring secondary outcomes reported that patients treated with disulfiram had significantly more days until relapse and fewer drinking days, respectively. The quality of the included studies was moderate. Heterogeneity was significant in most of the meta-analyses, but valid results were found regarding the effect of disulfiram versus placebo over 12 months and unsupervised disulfiram versus other or no treatment. The vast majority of significant studies were of shorter duration, while only 3 studies of 12 months were significant regarding more days until relapse and/or reduction in drinking days. Conclusions: Supervised treatment with disulfiram has some effect on short-term abstinence and days until relapse as well as number of drinking days when compared with placebo, none, or other treatments for patients with alcohol dependency or abuse. Long-term effect on abstinence has not been evaluated yet. However, there is a need for more homogeneous and high-quality studies in the future regarding the efficacy of disulfiram.