Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.