The objective of this review was to evaluate the efficacy of non-narcotic analgesics including non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol in the treatment of postoperative endodontic pain. Additionally, we aimed to examine the possible association of study covariates on the pain scores using meta-regression analysis. An electronic search was performed in 2016. After data extraction and quality assessment of the included studies (n=27, representing 2188 patients), meta-analysis was performed using a random-effect inverse-variance method. Meta-regression analysis was conducted to examine the associations between effect sizes and study-level covariates (P<0.05). The results showed that administration of non-narcotic analgesic was more effective than placebo in the management of postoperative pain, resulting in a lower pain scores with a standardized mean difference of -0.50 (95% CI= -0.70, -0.30), -0.76 (95%CI= -0.95, -0.56), -1.15 (95% CI= -1.52, -0.78), -0.65 (95% CI= -1.05, -0.26) for immediately after the procedure, 6-, 12-, and 24 h postoperative follow-ups (test for statistical heterogeneity: P=0.000,P=0.000,P=0.000,and P= 0.001), respectively. Our meta-regression analysis provided the evidence for association between some study covariates with treatment effect, each at different follow-ups. We concluded that the clinicians can manage postoperative endodontic pain by administration of NSAIDs and/or paracetamol. However, analgesics regimens should be considered as important determinants when prescribing a pharmacological adjuvant. This article is protected by copyright. All rights reserved.