A link between acute infections and the development of acute coronary syndromes (ACS) has been proposed. We used retrospective cohort and self-controlled case series analyses to define the closeness of the association between acute bacterial pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae and ACS. For the retrospective cohort analysis we included a control group of patients with admission diagnoses other than pneumonia or ACS. For the self-controlled case series analysis, we made within-person comparisons of the risk for ACS during the 15 days after admission for pneumonia with that of 365 days before and after that event. In 206 pneumonia patients (144 S. pneumoniae, 62 H. influenzae) we identified 22 (10.7%) cases of ACS, which compared to 6 (1.5%) among 395 controls resulted in an odds ratio (OR) of 7.8 (95% confidence interval [CI], 3.1-19.4). With multivariate logistic regression analysis, the OR for ACS in the pneumonia group remained elevated (OR, 8.5; 95% CI, 3.4-22.2). By the self-controlled case series method, the risk of ACS remarkably increased during the first 15 days after the diagnosis of pneumonia (incidence rate ratio, 47.6; 95% CI, 24.5-92.5). The characteristics and strength of these associations suggest a causal role for the acute infection in this relationship.