With the intention of reducing prophylactic antibiotic dosage, previous studies in the Zurich University Hospital have shown that a one/day prophylactic antimicrobial regimen with cefazolin was as effective as a single dose of ceftriaxone. In this prospective randomized study one day cefazolin prophylaxis (1 g q 8 h i.v.) was compared with a single dose of cefuroxime prophylaxis (1.5 g). In cases of cardiopulmonary bypass 0.75 g was added in the priming solution. In case of re-operation prophylaxis was repeated. 496 patients were enrolled in the study protocol; 78 patients were subsequently excluded. Of the remaining patients 224 (158 male, 66 female, mean age 61) were in the cefazolin group and 194 (142 male and 52 female, mean age 60) in the cefuroxime group. Mean duration of the intensive care unit (ICU) stay was three days in both groups and mean hospital stay was 16 days in the cefazolin group and 15 days in the cefuroxime group. The overall postoperative infection rate was 15.3%; 18.8% in the cefazolin group and 11.3% in the cefuroxime group. The statistical differences were found as in trend (p = 0.095). The lower incidence of infectious complications in the single cefuroxime dose group may indicate an improvement in effectiveness of antimicrobial prophylaxis: it offers patients a reliable antimicrobial protection. In addition, the single dose prophylaxis has the advantage of easier handling, reduced dosage frequency and lower cost.