ObjectiveTo review evidence from longitudinal studies on the association between prescription opioid use and common mood and anxiety symptoms.DesignWe conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.MethodsWe searched PubMed, Embase, and PsycINFO for search terms related to opioids AND (depression OR bipolar OR anxiety OR post-traumatic stress disorder [PTSD]). Findings were summarized narratively, and random-effects meta-analyses were used to pool effect sizes.ResultsWe identified 10,290 records and found 10 articles that met our inclusion criteria. Incidence studies showed that people who used prescription opioids had an elevated risk of any mood outcome (adjusted effect size [aES] = 1.80 [95% confidence interval = 1.40–2.30]) and of an anxiety outcome (aES = 1.40 [1.20–1.80]) compared with those who did not use prescription opioids. Associations with depression were small and not significant after adjustment for potential confounders (aES = 1.18 [0.98–1.41]). However, some studies reported an increased risk of depressive symptoms after increased (aES = 1.58 [1.30–1.93]) or prolonged opioid use (aES = 1.49 [1.19–1.86]).ConclusionsMental health should be considered when opioids are prescribed because some patients could be vulnerable to adverse mental health outcomes.