BACKGROUND: There is mounting pathologic and immunologic evidence that Chlamydia pneumoniae plays a role in the atherogenic pathway. However, very few clinical studies have supported these findings. METHODS: Using the administrative data of all patients > or =65 years of age who had an acute myocardial infarction (AMI) in Quebec between 1991 and 1995 (n = 26,195), we studied the relationship between the intake of antichlamydial antibiotics and post-AMI prognosis. Three groups were compared: patients exposed to (1) antichlamydial antibiotics, (2) sulfa-derivative antibiotics, to which C pneumoniae is not sensitive, and (3) neither of the above classes of antibiotics. Two periods of antibiotic exposure were explored: (1) during the first 3 months after AMI and (2) during the 6 months before AMI. RESULTS: Patients in the 3 exposure groups were similar except for a slightly lower proportion of men in the sulfa-derivative antibiotics group. Among all patients who were exposed during the 3 months after AMI and who survived at least 3 months, the 1-year mortality rate was similar across the 3 groups (10.1%, 11.1%, and 10.4% for the antichlamydial, sulfa-derivative, and nonexposed group, respectively) but favored the antichlamydial group at 2 years (15.9%, 23.0%, and 20.0%). In adjusted survival analysis, patients in the sulfa-derivative and nonexposed groups were slightly more likely to die than patients in the antichlamydial group (relative risk [RR], 1.38; 95% confidence interval [CI], 1.04 to 1.82 and 1.29; 95% CI, 1.05 to 1.59, respectively). Among individuals treated during the 6 months before AMI, the adjusted risk of dying was similar in the sulfa-derivative and nonexposed groups compared with the antichlamydial group (RR 1.03, 95% CI 0.90 to 1.18 and 1.08, 95% CI 0.99 to 1.19, respectively). CONCLUSIONS: Exposure to antichlamydial antibiotics during the 3 months after AMI is associated with a small survival benefit, whereas exposure during the 6 months before AMI does not affect survival.