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The purpose of this study was to evaluate the use of a 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid combination as a prophylactic therapy for the prevention of alveolar osteitis after mandibular third molar extractions and to investigate adverse reactions to chlorhexidine.This randomized, placebo-controlled, parallel group study was conducted in a group of 177 subjects, from which 3 groups were formed. The first group (n = 62) received 0.2% chlorhexidine gluconate, the second group (n = 56) received a 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid combination, and the third group (n = 59) received 0.09% sterile saline solution. All patients were recalled for the diagnosis of alveolar osteitis on the third and seventh postoperative days.When patients in the antibiotic group were compared with those in the other 2 groups, a significant reduction in alveolar osteitis was noted (P < .05). An alteration in taste, the bad taste of the solution, and staining of dentures and oral tissues were the major complaints about chlorhexidine.It would be more beneficial to use chlorhexidine solution with a β-lactamase inhibitor-containing antibiotic to enhance its effectiveness for the prevention of alveolar osteitis.