Objective:​ To test the hypothesis that bisphosphonates reduce AMI risk among new users and to assess whether the effect depends on the duration of treatment.

Methods:​ Case–control study nested in a primary cohort composed of patients aged 40 to 99 years, with at least 1-year registry in the BIFAP database throughout the study period 2002–2015. Out of this cohort, incident AMI cases were identified and five controls per case were randomly selected, matched by exact age, sex, and index date. The association of AMI with current, recent and past use of bisphosphonates was assessed by computing adjusted odds ratios (AOR) and their corresponding 95% confidence interval (CI) through an unconditional logistic regression. Only initiators of bisphosphonates were considered.

Results:​ A total of 23,590 cases of AMI and 117,612 controls were included. The mean age was 66.8 (SD 13.4) years, and 72.52% was male, in both groups. About 276 (1.17%) cases and 1458 (1.24%) controls were current users of bisphosphonates yielding an AOR of 0.98 (95% CI 0.854–1.14). Recent and past use were not associated with a reduced risk, either, nor was it found a reduction with treatment duration (AOR less than 1 year = 0.92;​ 95% CI 0.73–1.15;​ AOR more than 1 year = 1.03;​ 95% CI 0.86–1.23). Stratified analysis by age, sex and background cardiovascular risk did not show an effect modification by these variables.

Conclusion:​ The results do not support a cardioprotective effect of bisphosphonates regardless of the duration of treatment, age, sex or background cardiovascular risk. However, a small protective effect could have been masked if patients with osteoporosis have had a background higher risk of AMI.