Common mental disorders (CMDs) are highly prevalent in the working population, and are associated with long-term sickness absence and disability. Workers on sick leave with CMDs would benefit from interventions that enable them to successfully return to work (RTW). However, the effectiveness of RTW interventions for workers with a CMD is not well studied. The objective of this review is to assess the effectiveness of existing workplace and clinical interventions that were aimed at enhancing RTW. A systematic review of studies of interventions for improving RTW in workers with a CMD was conducted. The main outcomes were proportion of RTW and sick-leave duration until RTW. Randomized controlled trials (RCTs) were identified from Medline/PubMed, PsycINFO, EMBASE, SocINDEX, and Human resource and management databases from January 1995 to 2016. Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently homogeneous in different comparison groups and assessed the overall quality of the evidence. We reviewed 2347 abstracts from which 136 full-text articles were reviewed and 16 RCTs were included in the analysis. Combined results from these studies suggested that the available interventions did not lead to improved RTW rates over the control group [pooled risk ratio 1.05, 95% confidence interval (CI) 0.97–1.12], but reduced the number of sick-leave days in the intervention group compared to the control group, with a mean difference of −13.38 days (95% CI −24.07 to −2.69).