OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with higher risk for acute myocardial infarction (MI); but the post-infarction outcomes among these patients are unknown. Our objective was to compare post-acute MI outcomes in patients with SLE to those with diabetes mellitus (DM) and those with neither condition. METHODS: We analyzed the risk for prolonged hospitalization and in-hospital mortality following acute MI in the 1993-2002 US Nationwide Inpatient Sample. We used logistic regression to calculate odds ratios (OR) for prolonged hospitalization and Cox proportional hazards regression to calculate hazard ratios (HR) for in-hospital mortality with and without adjustments for age, sex, race/ethnicity, socioeconomic status, and presence of congestive heart failure. RESULTS: For the SLE (n = 2192), DM (n = 236,016), SLE/DM (n = 474), and control (n = 667,956) groups, the in-hospital mortality rates were 8.3%, 6.2%, 5.7%, and 4.7%, respectively. In multivariable regression models, all 3 disease groups had higher adverse outcome risk compared to control. The OR for prolonged hospitalization was higher for those with SLE (OR 1.48, 95% CI 1.32-1.79) compared to those with DM (OR 1.30, 95% CI 1.28-1.32). A similar pattern was observed for hazard ratios for in-hospital mortality as well (SLE, HR 1.65, 95% CI 1.33-2.04; DM, HR 1.11, 95% CI 1.07-1.14). CONCLUSION: SLE, like DM, increases risk of poor outcomes after acute MI. These patients need to be triaged appropriately for aggressive care.