In this comparative study, 150 consecutive patients undergoing local intraoral bone grafting randomly received either an oral single dose of 600 mg clindamycin or 2 g of the penicillin phenethicillin 1 h before incision. Primary endpoint was wound infection at the receptor site within 8 weeks of surgery. Secondary outcome measurements included postoperative infections at the donor site and adverse events as a result of antibiotic administration. Mean age of the patients was 36.8+/-12.7 years (range 18-67 years), and 98 patients were females (65.3%) and 52 males (34.7%). Infections at the receptor site were seen in 4 patients (5.3%; 95% CI 0.23-10.4%) of the phenethicillin group and in 2 patients (2.7%; 95% CI 0-6.36%) of the clindamycin group. In both groups, 3 patients had an infection at the donor site. Postoperative infections were predominantly caused by alpha-haemolytic Streptococci sensitive to penicillin. No significant difference was found between prophylactic single doses of phenethicillin and clindamycin with regard to postoperative infection in patients undergoing local bone augmentation procedures.