BACKGROUND The effect of extended prophylactic antibiotic therapy on postoperative infective complications such as wound infection and intra-abdominal abscess for non-perforated appendicitis is poorly defined. METHODS In a randomized controlled trial of 269 patients aged 15-70 years with non-perforated appendicitis undergoing open appendicectomy; 92 received single dose preoperative (group A), 94 received three-dose (group B) and 83 received 5-day perioperative (group C) regimens of cefuroxime and metronidazole. Postoperative infective complication was the primary endpoint. Secondary outcomes included length of hospital stay and complications related to antibiotic therapy. RESULTS The rate of postoperative infective complication was not significantly different among the groups (6.5% group A, 6.4% group B, 3.6% group C). The duration of antibiotic therapy had no significant effect on the length of hospital stay. Complications related to antibiotic treatment were significantly more common for 5-day perioperative antibiotic group (C) compared with single dose preoperative antibiotic group (A) (P = 0.048). CONCLUSIONS Single dose of preoperative antibiotics is adequate for prevention of postoperative infective complications in patients with non-perforated appendicitis undergoing open appendicectomy. Prolonging the use of antibiotics can lead to unnecessary antibiotic related complications.