Objective To evaluate the efficacy of single-dose antibiotic prophylaxis in transurethral resection of the prostate (TURP). Patients and methods A total of 139 patients were entered into a prospective randomized trial comparing single-dose antibiotic prophylaxis with no antibiotic before surgery. Twelve patients were excluded because they had significant bacteriuria before surgery (defined as ≥105 bacteria/mL). Of the remaining 127 patients, 62 were allocated to the single-dose group (A) and 65 to the no-antibiotic group (B). All 62 patients in group A received 1 g of ceftriaxone intravenously 1–2 h before surgery with the anaesthetic premedication, the 65 in group B receiving none. Urine cultures were collected post-operatively as the catheter was removed and again 4 weeks after hospitalization. Results The incidence of post-operative bacteriuria was statistically significantly different, occurring in five patients (9%) in group A and 16 patients (26%) in group B (Fisher’s exact test, one-tail P=0.009). There was no significant difference between the groups 4 weeks after hospitalization. The overall incidence of bacteriuria post-operatively and 4 weeks after hospitalization was 11 patients (18%) in group A and 22 patients (34%) in group B (P=0.03). Conclusion Single-dose antibiotic prophylaxis with 1 g of ceftriaxone intravenously is effective in patients undergoing TURP and is recommended for such surgery.