The literature provides no guidelines for antibiotic use in palatoplasty. The authors sought to ascertain practice patterns; review a large, single-surgeon experience, and propose guidelines for antibiotic use in primary palatoplasty. A six-question survey was e-mailed to all surgeons of the American Cleft Palate-Craniofacial Association. A retrospective study was also conducted of the senior author's 10-year primary palatoplasty series, and two groups were studied. Group 1 received no antibiotics. Group 2 received preoperative and/or postoperative antibiotics. Three hundred twelve of 1115 surgeons (28 percent) responded to the survey. Eighty-five percent administered prophylactic antibiotics, including 26 percent who used a single preoperative dose. A further 23 percent gave 24 hours of postoperative therapy; 12 percent used 25 to 72 hours, 16 percent used 4 to 5 days, and 12 percent used 6 to 10 days. Five percent of surgeons administered penicillin, 64 percent administered a first-generation cephalosporin, 13 percent administered ampicillin/sulbactam, and 8 percent gave clindamycin. The authors reviewed 311 patients; 173 receive antibiotics and 138 did not. Delayed healing and fistula rates did not differ between groups: 16.8 percent versus 15.2 percent (p = 0.71) and 2.9 percent versus 1.4 percent (p = 0.47), respectively. A single patient treated without antibiotics developed a postoperative bacteremia. This case did not meet the Centers for Disease Control definition of a surgical site infection, but the patient developed a palatal fistula. Antibiotic use in primary palatoplasty varies widely. The authors' data support a clinician's choice to forego antibiotic use; however, given the significance of palatal fistulae and the single case of postoperative streptococcal bacteremia, the study group recommends a single preoperative dose of ampicillin/sulbactam. Current evidence cannot justify the use of protracted antibiotic regimens. Therapeutic, III.