AIMS: The aim of the present study was to investigate whether use of specific antibiotic drugs decreases the risk of coronary heart disease in diabetes mellitus type 2 patients. METHODS AND RESULTS: Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and hospitalizations for all 450,000 residents of eight Dutch cities. In a nested case-control study among diabetes mellitus type 2 patients, 244 cases with a first hospitalization for coronary heart disease and 686 controls without coronary heart disease matched on age, sex, calendar time, and registration date in PHARMO RLS were selected. Use of antibiotic drugs among cases and controls was determined over 3 years prior to the event. Use of fluorquinolones for more than 14 days compared to no use of fluorquinolones was associated with a lower risk of coronary heart diseases (OR(adj)=0.30 (95%CI: 0.12-0.75)). No association between tetracycline, macrolide and lincosamide treatment, or other antibiotic drugs (penicillins, cephalosporines, sulphonamides and trimethoprim), and the risk of coronary heart disease was found. CONCLUSION: Our results suggest that treatment with fluorquinolones in doses commonly prescribed in routine clinical practice is associated with a reduction in the risk of coronary heart diseases among diabetes mellitus type 2 patients.