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Musculoskeletal disorders (MSDs) are a common source of work disability. Opioid prescribing for MSDs has been on the rise, despite a lack of data on effectiveness. The objective of this study was to conduct a systematic review to determine whether early receipt of opioids is associated with future work outcomes among workers with MSDs compared with other analgesics, no analgesics, or placebo.MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from inception to 2014 and reference lists were scanned. Studies were included if opioids were prescribed within 12 weeks of MSD onset. Eligible outcomes included absenteeism, work status, receiving disability payments, and functional status. Two reviewers independently reviewed articles for relevance, risk of bias, and data extraction using standardized forms. Data synthesis using best evidence synthesis methods was planned.Five historical cohort studies met the inclusion criteria, all including workers filing wage compensation claims. Four studies demonstrated a significant association between early opioids and prolonged work disability. One study found a shorter time between prescriptions to be associated with shorter work disability. However, all studies were found to be at a high risk of bias and a best evidence synthesis could not be conducted. The main limitations identified were with exposure measurement and control of confounding.Current literature suggests that opioids provided within the first 12 weeks of onset of an MSD are associated with prolonged work disability. However, the conclusions of these studies need testing in a high-quality study that addresses the methodological shortcomings identified in the current review.