The aim of this study was to examine the effect of antibiotic prophylaxis for mandibular third molar surgery from the viewpoint of the duration of administration. A comparative study was conducted on postoperative infection, dry socket, and the healing process in 178 healthy patients receiving 1-day or 3-day prophylaxis with lenampicillin (LAPC; 1.5g/day). Postoperative infection developed in only 1 (1.1%) of the 91 patients in the 3-day group, while there was no patient with infection in the 87 patients in the 1-day group. Dry socket developed in 8.0% of the 87 patients in the 1-day group and in 7.7% of the 91 patients in the 3-day group. However, the incidence of these complications, in relation to the degree of impaction of the molars, did not significantly differ between the 1-day and 3-day groups. Scores indicating clinical symptoms for the 7 days after surgery also reflected no significant difference between the groups, irrespective of the degree of impaction. These results suggest that 1-day therapy with LAPC in our regimen may at least be recommended as a prophylaxis for mandibular third molar surgery in medically healthy patients.