Objective To determine the efficacy of antibacterial prophylaxis in preventing infectious complications after percutaneous endoscopic gastrostomy. Design Prospective, randomised, placebo controlled, double blind, multicentre study. Setting Departments of internal medicine at six German hospitals. Subjects Of 106 randomised adult patients with dysphagia, 97 received study medication, and 84 completed the study. The median age of the patients was 65 years. Most had dysphagia due to malignant disease (65%), and many (76%) had serious comorbidity. Interventions A single intravenous 2.2 g dose of co-amoxiclav or identical appearing saline was given 30 min before percutaneous endoscopic gastrostomy performed by the thread pull method. Main outcome measures Occurrence of peristomal wound infections and other infections within one week after percutaneous endoscopic gastrostomy. Results The incidence of peristomal and other infections within one week after percutaneous endoscopic gastrostomy was significantly reduced in the antibiotic group (8/41 (20%) v 28/43 (65%), P < 0.001). Similar results were obtained in an intention to treat analysis. Several peristomal wound infections were of minor clinical significance. After wound infections that required no or only local treatment were excluded from the analysis, antibiotic prophylaxis remained highly effective in reducing clinically important wound infections (1/41 (2%) v 11/43 (26%), P < 0.01) and non-wound infections (2 (5%) v 9 (21%), P < 0.05). Conclusions Antibiotic prophylaxis with a single dose of co-amoxiclav significantly reduces the risk of infectious complications after percutaneous endoscopic gastrostomy and should be recommended.