Background: The purpose of this systematic review was to determine the risk of alveolar osteitis with the use of traditional non-steroidal anti-inflammatory analgesics (NSAIDs) and COX-2 selective inhibitors compared to placebo using data from published clinical trials. Material and Methods: Embase and Medline/PubMed databases were employed to search for clinical trials. Articles that met the inclusion criteria were assessed for risk of bias using the Cochrane tool and data on alveolar osteitis were specifically extracted. Statistical analysis was performed using Review Manager 5.3 software. Results: The risk assessment for alveolar osteitis concerning traditional NSAIDs included 19 clinical trials (n=2888) while for COX-2 inhibitors included 13 clinical trials (n=3820). Overall statistical analysis and subgroup evaluation by medication indicated that traditional NSAIDs did not increase the risk of alveolar osteitis. On the other hand, subgroup statistical analysis for selective COX-2 inhibitors suggested that rofecoxib elevated a patient's risk of developing alveolar osteitis (n=947, I2=0%, Z=2.52, OR=1.89, 95% CI=1.15 to 3.10, p=0.01) compared with placebo. Sensitivity analysis of the rofecoxib data exhibited high statistical robustness. Conclusions: Data indicates that rofecoxib increases the risk of alveolar osteitis in patients undergoing tooth extraction.