Objectives: Alveolar osteitis (AO) is the most common complication following tooth extraction. This study aims to evaluate the effect of topical clindamycin on AO prevention. Methods: This double-blind randomized clinical trial was conducted on 300 patients (59% male, 41% female; age: 18-68 years) requiring tooth extraction. The information including age, gender, taking oral contraceptive pill (OCP), smoking, tooth type, tooth growth status, tooth location, and extraction modality were collected. Patients were randomized into two equal groups: experimental group (clindamycin biodegradable dressing) and control group (placebo biodegradable dressing) .The dressings were placed in alveolar sockets following extractions. Patients were examined for signs of AO on third and seventh days. Data were analyzed by SPSS.18 using log-binomial regression. Results: The overall incidence of AO was 5.7%. AO occurrence was not significantly different between experimental (5.3%) and control (6%) groups (OR=0.889; P=0.803). Female gender (OR=3.454; P=0.017), OCP use (OR=3.857; P=0.013), mandibular location (OR=4.081; P=0.012), and surgical extraction (OR=2.788; P=0.042) were significantly associated with AO development. AO merely occurred in non-smokers. Lower age (OR=2.75; P=0.32) and tooth impaction (OR=2.059; P=0.185) had no significant effect. All cases of AO presented on the day seven. Conclusions: Clindamycin biodegradable dressing does not significantly reduce the risk of AO. Therefore, topical clindamycin is not justified as prophylactic agent.