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To systematically review studies of Mycoplasma genitalium and the association with HIV infection in adults and to summarize the findings in a meta-analysis.A systematic review and meta-analysis.Epidemiological studies of the association of M. genitalium and HIV infection published prior to June 2008 were identified in a systematic review of the published literature. A random-effects meta-analysis was used to calculate the summary odds ratio (OR) and 95% confidence interval (CI). Further analyses stratified by geographical area and type of control population, and sensitivity analyses were conducted to assess between-study heterogeneity and publication bias.Nineteen eligible studies were identified. The prevalence of M. genitalium ranged from 3.1% to 47.5%. Seventeen studies found that participants with M. genitalium were more likely to be HIV infected, and this association was statistically significant in 12 studies. The summary odds ratio (OR) was 2.01 [95% confidence interval (CI) = 1.44–2.79]. The association was stronger in sub-group analyses among studies in sub-Saharan Africa (OR = 2.60, 95% CI = 2.17–3.11) and studies with healthy control populations (OR = 2.57, 95% CI = 2.05–3.22). There was strong evidence of between-study heterogeneity among all studies combined; however, between-study heterogeneity was substantially reduced in sub-group analyses. There was no statistical evidence of publication bias.The strong association between M. genitalium and HIV infections in these primarily cross-sectional observational studies highlights the need for longitudinal studies to understand the temporal association between these infections. Testing and treatment of M. genitalium-positive individuals in high-risk populations should be investigated as a potential HIV prevention strategy.