Summary Background : Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. Aim : To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. Methods : One hundred and forty‐one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n = 50) or placebo (n = 51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0–3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. Results : Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P = 0.04 and 0.03, respectively. Conclusion : Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.