OBJECTIVE To evaluate the efficacy and safety of piperacillin in the prevention of perioperative febrile morbidity in elective cesarean sections, a combination of cephradine plus metronidazole vs. a control group which did not receive any antibiotic prophylaxis. METHODS 198 women undergoing elective cesarean section were included in a randomized control study to compare the prophylactic efficacy and safety of a single dose (4 g) or three doses (2 g) of piperacillin, three doses of cephradine plus metronidazole combination, when administered peri-operatively and a control group which did not receive prophylactic antibiotics. RESULTS 198 women were randomized to the study, but 14 had to be excluded leaving 184 for analysis. Statistically significant difference was reached when comparing the piperacillin groups (group A and group C) with control (group D) in the prevention of postoperative febrile morbidity inclusive of wound infection and endomyometritis (single-dose piperacillin group A: Relative Risk = 0.14, 95% CI 0.03-0.58). Multi-dose piperacillin therapy group C: R.R. = 0.27, 95% CI 0.10-0.77). The combination of cephradine and metronidazole (group B) when compared with the control group did not show any statistical significant difference in prevention of postoperative febrile morbidity (R.R.= 0.49, 95% CI 0.22-1.10). Single-dose piperacillin when compared to multi-dose piperacillin regimen appears to be more effective at reducing postoperative infective morbidity but this is not statistically significant (R.R. = 0.51, 95% CI 0.10-2.65). When febrile morbidity is separated into wound infection and myometritis, the reduction rates in either of them in each antibiotic study group A, B and C compared to the control group D are not significant except when study groups A and C are combined and compared to control group D (R.R. = 0.21, 95% CI 0.76-0.06). CONCLUSIONS Piperacillin single agent therapy, either as a single dose of 4 g or a triple dose of 2 g, is effective and safe in the prevention of postoperative infection when given as prophylaxis in elective cesarean cases.