Objective: To assess the effect and safety of pre-emptive oral nonsteroidal anti-inflammatory drugs (NSAIDs) for the success of inferior alveolar nerve block (IANB) in irreversible pulpitis treatment. Method and Materials: Medline (via OVID, 1948 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2011), EMBASE (via OVID, 1984 to July 2011), Chinese BioMedical Literature Database (1978 to July 2011), China National Knowledge Infrastructure (1994 to July 2011), and WHO International Clinical Trials Registry Platform were searched electronically. In addition, relevant journals as well as reference lists of included studies were hand searched for randomized clinical trials comparing the effect or safety of NSAIDs in irreversible pulpitis treatment. Risk of bias assessment with the Cochrane collaboration tool and data extraction were independently performed by two reviewers. Metaanalysis was delivered with RevMan 5.1. Results: Seven studies were included. Six of them had low risk of bias, and one had an unclear risk of bias. A dosage of 600 to 800 mg of ibuprofen showed a significant effect in increasing the success rate of IANB (relative risk [RR], 1.52; 95% confidence interval [CI], 1.17 to 1.98; P = .002), and the results were moderately reliable. A dosage of 75 mg of indomethacin had a significant effect compared to a placebo (RR, 1.94; 95% CI, 1.22 to 3.06; P = .005), as did 8 mg of lornoxicam (RR, 2.80; 95% CI, 1.59 to 4.93; P = .0004) and 50 mg of diclofenac potassium (RR, 2.40; 95% CI, 1.34 to 4.31; P = .003). Other NSAIDs such as ketorolac, ibuprofen and acetaminophen together, and acetaminophen alone showed no statistical significance compared to the placebo. No serious adverse events were reported. Conclusion: The clinical evidence suggests that pre-emptive oral NSAIDs might have a good effect and are safe in increasing the success rate of IANB, but more studies are necessary to confirm such outcomes. Keywords: anesthesia, anti-inflammatory agent, meta-analysis, nonsteroidal, pulpitis