We prospectively studied Enterobacter colonization in cardiac surgery patients receiving cefazolin prophylaxis. Fifty-eight (67%) of 87 patients became colonized, 28 by the time of admission to a Cardiac Surgery Intensive Care Unit. Enterobacter cloacae was four times more prevalent than Enterobacter aerogenes. We found increased Enterobacter colonization, after prophylaxis, in 45% of surgery patients. None of 25 control patients, who underwent coronary angioplasty and received no antibiotic prophylaxis, showed increased colonization (P = .001). Both groups had similar baseline rates of Enterobacter carriage. Typing showed 50 distinct strains of E. cloacae and 11 of E. aerogenes; 25% of patients carried greater than or equal to 2 strains simultaneously. In the nine cases of horizontal transmission, source patients were intubated for greater than or equal to 5 days and had heavy throat carriage of Enterobacter. No environmental sources of transmission were found. Clinical Enterobacter infection developed in 12 patients; at least nine of these were infected with a strain that had been isolated by surveillance culture. We conclude that Enterobacter, part of the patients' endogenous flora, becomes an important pathogen when amplified by prophylactic antibiotics and is less often transmitted horizontally.