We conducted a prospective, double-blind, placebo-controlled study in adult patients to determine whether prophylactic penicillin prevents infection in intraoral lacerations secondary to minor trauma or seizures. Uninfected full-thickness, mucosal-only, or through-and-through wounds presenting within 24 hours of injury were considered. Management consisted of cleansing, irrigation, debridement, and closure as indicated: no topical antibiotics were applied. Patients were randomly assigned to receive penicillin VK 500 mg or identically appearing placebo four times daily for five days. Home wound care was standardized and patients were followed for a minimum of four or five days. Infection was assessed clinically. Seventy-six patients were enrolled and 62 completed the study. Penicillin (30) and placebo (32) groups were similar in all parameters except wound etiology; assault was more common in the placebo group (P = .02). Two infections occurred in patients receiving penicillin, and six infections were seen among placebo-treated patients (P = .05, beta = 0.17). When patients poorly compliant with therapy were eliminated from analysis, none of the penicillin-treated patients and five of the placebo-treated patients developed infections (P = .027). Our data suggest that patients with intraoral wounds may benefit from prophylactic penicillin if compliant with their therapy. More studies are needed to further delineate the usefulness of prophylactic antibiotics for these wounds.