OBJECTIVE: To determine the effect of the number of different drugs with adherence to medication of at least 70% on recurrent admission for myocardial infarction (MI) in patients with a history of MI. DESIGN: Nested case-control study in a dynamic cohort. SETTING: PHARMO database that contains pharmacy dispensing records and hospital discharge records of 350,000 Dutch citizens. SUBJECTS: All patients admitted to hospital for first MI (ICD-9 410) from 1991 to 2000 with at least a 30-day survival after admission. Cases were admitted for recurrent MI and were matched for age, sex, and year of admission with controls who did not have a recurrent MI. MAIN OUTCOME MEASURE(S): Odds ratio with 95% CI for admission for recurrent MI. Exposure was the number of preventive drugs (antiplatelet agents, statins and beta blockers or ACE inhibitors) used for at least 70% of the time. RESULTS: 389 cases were matched with 2344 controls. The use of one drug was associated with a 6% odds reduction (95% CI 30% reduction to 28% increase) for admission for recurrent MI. The use of two or three drugs was associated with reductions of 26% and 41% (47% reduction to 3% increase and 6% to 63% reduction, respectively). Addition of one drug caused a 16% reduction (4% to 26%). CONCLUSIONS: Multiple drug treatment decreases admissions for recurrent MI in patients with a history of MI. Every addition of a drug, regardless of drug class, reduces the risk even further. These results support the treatment strategies as applied in daily practice.