Effectiveness of NSAIDs premedication following third molar extraction: a systematic review with meta-analysis of randomized clinical trials

Third molar extraction is one of the most common procedures in oral surgery and is frequently associated with postoperative pain, edema, and trismus. In this context, this systematic review aimed to evaluate the effectiveness of premedication with non-steroidal anti-inflammatory drugs (NSAIDs) on postoperative outcomes following this procedure. A systematic review was conducted in accordance with the Cochrane guidelines and the PRISMA statement, with the protocol registered in PROSPERO (CRD420251048164). Randomized controlled trials including healthy adults undergoing third molar extraction under local anesthesia were included. NSAID premedication was compared with placebo or no premedication, with both groups following standardized postoperative rescue medication protocols. Searches were performed in PubMed, Embase, Web of Science, and EBSCO from inception to April 2025. The risk of bias was assessed using the Cochrane RoB-1 tool, and the certainty of the evidence was evaluated using the GRADE approach. Random-effects meta-analyses were conducted using standardized mean differences (SMD) and risk ratios (RR). Fifteen randomized controlled trials involving 779 participants were included. NSAID premedication significantly reduced postoperative pain within the first 4 h (SMD = -1.20), between 5 and 12 h (SMD = -0.75), at 24 h (SMD = -1.42), and at the longest follow-up periods (SMD = -1.25). It also reduced rescue medication consumption (SMD = -0.63) and the risk of rescue medication use by 39% (RR = 0.61). NSAID premedication reduces postoperative pain and the need for rescue medication after third molar extraction, with a favorable safety profile, supporting its clinical use despite the low certainty of the evidence.