Wound infections are a major problem in burned patients. To determine the rate of wound infection associated with initial wound size and the amount of open full-thickness wound, we prospectively studied all patients admitted within 1 week of burn injury during a 2-year period using weekly wound cultures. Wounds were treated with topical silver sulfadiazine and occlusive dressings. Burn wound excision and immediate grafting were initiated during the first postburn week. One thousand five hundred twenty-three patient weeks (483 patients) were evaluated. Serious burn wound infections developed during 55/185 patient weeks (42.3%) when the initial total burn (ITB) was greater than 40% body surface area (BSA). This decreased to 27/304 (8.9%) when the ITB was 21% to 40% and 60/1034 (5.8%) when the ITB was less than 20% BSA. Burn wound infections developed during 57/211 patient weeks (27.0%) when the initial full-thickness burn (IFB) was greater than 20% BSA. The rate of wound infection decreased to 73/776 (9.4%) when the IFB was 1% to 20% and to 12/536 (2.2%) when no IFB was present. We further analyzed the prevalence of serious wound infections in relation to the open wound size during the hospital course. Wound infections occurred during 47 of 96 patient weeks (49.0%) when the current full-thickness wound was greater than 10% BSA. The infection rate decreased to 76 of 594 (12.8%) and 17 of 833 patient weeks (2.0%) when the remaining full-thickness wound was reduced to 1% to 10% and less than 1% BSA, respectively (p less than 0.05). Early wound closure would appear to reduce the risk of serious wound infections, especially in patients with full-thickness burns.