We explored the association between diagnosed rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and the risk of developing a first-time acute myocardial infarction (AMI) by conducting a population-based, case-control analysis using data from the United Kingdom-based General Practice Research Database (GPRD). Among 8,688 patients with AMI and 33,329 matched controls, the adjusted odds ratio (ORs) of AMI for subjects with RA was 1.47 (95% confidence interval [CI] 1.23 to 1.76), and in subjects with both RA and diagnosed hyperlipidemia, the OR was 7.12 (95% CI 4.16 to 12.18). The risk associated with SLE was 2.67 (95% CI 1.34 to 5.34). These results underline that RA and SLE increase the risk of AMI.