A prospective study was undertaken to identify potential sources of infection in patients requiring open heart surgery. Preoperative blood and urine cultures were sterile. Cultures done during surgery were positive in 47 (71%) of 66 patients studied. The most common site of microbial contamination was the repaired area of the myocardium and the prosthesis just prior to wound closure; diphtheroids and Staphylococcus epidermidis were the most frequent operative isolants. Postoperative blood cultures were sterile; however, 41% of urinary catheter tips and 50% of intravascular catheter tips yielded a variety of Gram-positive and Gram-negative organisms and fungi. Endocarditis was not encountered despite the high incidence of perioperative contamination by organisms that commonly cause postoperative infective endocarditis. (JAMA 230:1415-1418, 1974)