When we noticed an increasing incidence of deep sternal surgical site infections (DSSI), a bundle of interdisciplinary infection control measures was initiated in order to prevent further cases of DSSI. Adherence to infection control measures was re-inforced, which included (1) methicillin-resistant Staphylococcus aureus (MRSA) screening, (2) bacterial decolonisation measures, (3) hair clipping instead of shaving, (4) education, (5) good stewardship for antibiotic prophylaxis, (6) change of surgical gloves after sternotomy and after sternal wiring, (7) new bandage techniques, (8) leaving the wound primarily covered for at least 48 h. We checked for potential risk factors in a case-control study (120 patients each) by multivariate analysis. A significant decrease of DSSI from 3.61% (CI 95: 2.98-4.35) down to 1.83% (CI 95: 1.08-2.90) occurred. Independent significant risk factors for DSSI were age >68 years (OR=2.47; CI 95: 1.33-4.60), diabetes mellitus (OR=4.84; CI 95: 2.25-10.4), and intra-operative blood glucose level >8 mmol/l (OR=2.27; CI 95: 1.17-4.42). Protective factors were preoperative antibiotic prophylaxis (OR=0.31; CI 95: 0.13-0.70) and extubation on the day of surgery (OR=0.25; CI 95: 0.11-0.55). Close co-operation between clinical physicians and the infection control team significantly reduced the rate of DSSI. Thus, cardiac surgeons should know the local baseline DSSI rate, e.g. by surveillance, and should be aware of the risk factors for DSSI cases.