One of the most common oral procedures carried out every day in oral and maxillofacial surgery units is the surgical removal of impacted mandibular third molars. After the impacted mandibular third molar has been removed, postoperative morbidity is unavoidable. Alveolar osteitis, a painful, unhealed socket, is one of the most frequent surgical sequelae. By introducing and applying a new material inside the extraction socket, many researches were attempted to prevent the development of alveolar osteitis. This study aims to make a comparison between the effect of the locally applied Doxycycline and the systemic Doxycycline on the occurrence of alveolar osteitis after surgical removal of impacted mandibular third molars. A randomized prospective clinical study was conducted on 50 patients who had undergone surgical removal of impacted mandibular third molars under local anesthesia. The patients were distributed in 2 groups: Study group; included 25 patients treated by local application of Doxycycline inside the socket immediately after surgical removal of impacted tooth. Control group: consisted of 25 patients who received systemic Doxycycline one hour before surgical removal of impacted tooth. Alveolar osteitis was evaluated on the 2nd and 7th day after surgery. There was a significant reduction of alveolar osteitis in the study group in comparison to the control group (p< 0.05). The local application of Doxycycline significantly reduces the incidence of alveolar osteitis.