OBJECTIVE: To determine the effect of clindamycin in the prevention of infection after oral surgery. MATERIAL AND METHODS: This systematic review and meta-analysis followed the PRISMA statement, the PICO-framework and included only randomized controlled clinical trials. In all studies clindamycin was administered to prevent infections in patients who underwent oral surgery. Two independent researchers conducted the search, data extraction and risk of bias assessment. Included studies were classified by the type of oral surgery. Besides, data of patients, procedures and outcome variables were collected. Risk ratios (RR) and 95% confidence intervals (CI) were calculated by using Mantel-Haenszel model and the number needed to treat (NNT). Finally, any potential sources of heterogeneity were estimated. RESULTS: Seven trials of 540 articles met the inclusion criteria and were included in the qualitative synthesis. Four articles assessing the effect of oral clindamycin in third molar surgery were quantitatively analyzed. The overall RR was 0.66 (95% CI = 0.38-1.16), being non-statistically significant (p = 0.15). There was no heterogeneity between the studies I = 0, p = 0.44. The NNT was 29 (95% CI = 12- -57). CONCLUSIONS: The effectiveness of clindamycin could not be evaluated except in third molar extraction. Oral clindamycin is ineffective in preventing infection in third molar surgery. CLINICAL RELEVANCE: There is a lack of high-quality evidence supporting the prescription of clindamycin to prevent infections after oral surgery, despite being frequently prescribed as an alternative for penicillin-allergic patients. Oral clindamycin has not been shown to be effective after third molar extractions.