IMPORTANCE Biologic therapies are widely prescribed immunomodulatory agents. There are concerns that compared with treatment with conventional systemic therapy, long-term biologic treatment for common immune-mediated inflammatory diseases, namely inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriasis, may be associated with increased risk of melanoma.OBJECTIVE To examine whether biologic treatment of IBD, RA, or psoriasis is associated with an increased risk of melanoma compared with conventional systemic therapy.DATA SOURCES Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published from January 1, 1995, to February 7, 2019, for eligible studies.STUDY SELECTION Randomized clinical trials, cohort studies, and nested case-control studies quantifying the risk of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with patients treated with conventional systemic therapy were included.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted key study characteristics and outcomes. Study-specific risk estimates were pooled, and random-and fixed-effects model meta-analyses were conducted. Heterogeneity was assessed using the I 2 statistic. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. MAIN OUTCOMES AND MEASURESThe pooled relative risk (pRR) of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with biologic-naive patients treated with conventional systemic therapy. RESULTSSeven cohort studies comprising 34 029 biologic-treated patients and 135 370 biologic-naive patients treated with conventional systemic therapy were eligible for inclusion. Biologic treatment was positively associated with melanoma in patients with IBD (pRR, 1.20; 95% CI, 0.60-2.40), RA (pRR, 1.20; 95% CI, 0.83-1.74), or psoriasis (hazard ratio, 1.57; 95% CI, 0.61-4.09) compared with those who received conventional systemic therapy, but the differences were not statistically significant. Adjustment for other risk factors was absent from most studies. CONCLUSIONS AND RELEVANCEThe findings suggest that clinically important increases in melanoma risk in patients treated with biologic therapy for common inflammatory diseases cannot be ruled out based on current evidence. However, further studies with large patient numbers that adjust for key risk factors are needed to resolve the issue of long-term safety of biologic therapy.