The efficacy of perioperative antibiotic prophylaxis in cesarean section with a single dose of ceftriaxone, a long-acting cephalosporin not widely used for prophylaxis, was tested. Ceftriaxone as a single dose of 1 g i.v. versus three doses of cefoxitin 1 g i.v. respectively were used in a prospective, randomized, controlled study consisting of 1052 patients undergoing cesarean section. Postoperative infection rate as measured by fever, endometritis and wound infection was 6.5% with ceftriaxone and 6.4% with cefoxitin. Urinary tract infections were significantly more frequent in the cefoxitin than in the ceftriaxone group (17.8% vs. 9.7%, p < 0.001). Enterococci and Escherichia coli accounted for urinary tract infections 1.86-, respectively, 4.3-fold more frequently with cefoxitin than with ceftriaxone. The time of hospitalization in patients with urinary tract infections was significantly lower with ceftriaxone than with cefoxitin (11 vs. 12 days, p < 0.05). The tolerance in both groups was equally satisfactory. A single dose of ceftriaxone, which is simple, reliable (compliance), well tolerated, inexpensive (fewer urinary tract infections and therefore fewer treatment costs than with cefoxitin) and safe (no overgrowth of pathogens) in our opinion is the antibiotic regimen of choice for prophylaxis in cesarean section in the described circumstances.