The purpose of this prospective, randomized, comparative clinical study was to compare treatment outcome of removal of foci and incision and drainage, with or without oral antibiotic therapy, in the management of single primary maxillofacial space infection with a known focus.A total of 40 patients with single primary maxillofacial space infection with a known infectious focus were divided into two groups, one treated with incision and drainage only, and the other with incision and drainage along with oral antibiotics. The focus of infection was addressed in both groups. Parameters evaluated included pain score, maximum mouth opening, swelling, purulent discharge and return to normal life, which were assessed on days 1, 2, 3, 5 and 7. The patients were followed up until they reported return to normal life as assessed by a questionnaire.All of the patients rapidly responded to treatment as observed by a reduction in pain, swelling, discharge, and improvement in mouth opening. Pus discharge stopped within first 3 days in 75% of patients. The patients who underwent immediate extraction showed a faster resolution of infection (mean return to normal life = 9 days) than others (mean = 11.2 days). There was no statistically significant difference between the two groups for the five study parameters (p < 0.05). Of the total pus specimens, 75% had no significant bacterial growth, or grew 'oral flora'/contaminants, while only 25% grew specific bacteria.This study questions the conventional practice by dental practitioners and surgeons of prescribing antibiotics to all patients with odontogenic infection. Microbial culture and antibiotic sensitivity is of little therapeutic value in selected patient groups.