To define the outcome of treatment for deep sternal wound infections (DSWIs) using direct wound closure (DC) or vacuum-assisted therapy (VAT) based on negative vs. positive microbiological results. Between 1999 and 2008, 7746 patients underwent median sternotomy for cardiac surgery at our institution. Patients were screened for DSWI and out of the cohort 159 were identified (2%). These patients were treated, either using DC or VAT with delayed wound closure. Outcomes were retrospectively analysed to determine the effect of negative cultures at the time of closure. The indication for sternotomy was CABG 51%, isolated valve 18%, CABG/valve 18% and other related cardiovascular procedures 14%. Sixty-five percent of the wound infections was diagnosed during rehabilitation period. One hundred and five (66%) patients were treated with VAT vs. 54 (34%) patients with direct closure. Coagulase negative staphylococci were found in 48% of bacterial cultures. In 75% of the patients, the microbiological results were positive at time of wound closure (69.2% VAT vs. 87.0% direct closure, P = 0.014). Out of 159 patients, 5.0% were with positive microbiological results at the time of closure readmitted vs. 5.1% with negative microbiological results (P = 1.0). Patients with VAT stayed significantly longer in the hospital (mean 21 ± 16 vs. 13 ± 12, P = 0.002). Negative microbiological results are not mandatory before wound closure, as the rate of readmissions for recurrence of infection showed no difference between groups. Our results also suggest that shortening of VAT despite positive microbiological results may be feasible.