49 patients with severe infectious complications of midsternotomy incision were treated at our referral center over a 3-year period. 43 species of microorganisms were identified in 38 patients, the most common being Pseudomonas aeruginosa (37 % and Staphylococcus aureus (30% Most of the patients underwent aggressive debridement and chest wall reconstruction by muscle transposition in combination with antimicrobial therapy. Antimicrobial therapy was given perioperatively according to the in vitro susceptibility of the organisms. Treatment was continued beyond this period for 2-3 weeks in patients with extensive deep seated infection or in those with positive cultures from intraoperative specimens. Some patients needed a longer course of up to 6-8 weeks antimicrobial therapy because of insufficient response to the shorter course. In all, 45/49 patients had complete wound healing. 28 recovered within 2-5 weeks and 16 required a more protracted course with additional surgery in 8; 1 wound did not heal after 20 months and 4 patients died from non-infectious complications. Due to the lack of specific guidelines in the literature as to the proper choice and length of administration of antimicrobial therapy for midsternotomy wound infection, and in view of these favorable results, we recommend our protocol in the treatment of midsternotomy wound infection (in combination with appropriate surgery).