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Persons living with HIV (PLWH) are at greater risk for acute coronary syndrome (ACS). Practice patterns of ACS management by HIV serostatus are unknown. We examined the presentation and management of ACS in PLWH.Retrospective case–control study.We included 86 PLWH and 263 sex-matched and race-matched HIV-negative controls hospitalized with ACS between 2004 and 2013. We performed multivariable conditional logistic regression to determine the associations between HIV serostatus and ACS type and management.Both groups were predominantly of black race and male sex. PLWH were significantly younger (53 vs. 60 years) and more likely to smoke (48 vs. 31%). Among PLWH, 30% had CD4+ cell count less than 200 cells/μl and 58% had undetectable HIV RNA. PLWH had more single-vessel disease and a higher median Gensini score among those with single-vessel disease (32 vs. 4.25) than controls. HIV serostatus was positively associated with ST-elevation myocardial infarction (STEMI) [adjusted odds ratio (aOR) (95% confidence interval (CI)):5.05 (1.82–14.02)], and any revascularization procedure after ACS [aOR (95% CI): 2.90 (1.01–8.39)] and negatively associated with non-STEMI [aOR (95% CI): 0.33 (0.14–0.79)] presentation. PLWH who underwent stent placement had a higher likelihood of bare metal stent placement compared with controls [70 vs. 15%, aOR (95% CI): 5.94 (1.33–26.55)]. Among PLWH, ACS characteristics were not significantly associated with CD4+ cell count, HIV RNA, or antiretroviral therapy.PLWH hospitalized with ACS were more likely to have severe single-vessel disease, present with STEMI rather than non-STEMI, and undergo revascularization, and less likely to have a drug-eluting stent placed than matched HIV-negative controls, suggesting that coronary plaque morphology and/or distribution is different with HIV infection and warrants further investigation.