This systematic review aimed to analyze the efficacy of corticosteroid premedication compared to placebo or no treatment to reduce postoperative pain in endodontic patients. Randomized controlled trials (RCTs) assessing corticosteroids via oral, intramuscular, subperiosteal, intraligamentary or intracanal route compared to passive or active placebo, or no treatment were included. Four databases were searched: PubMed, Web of Science, Cochrane Library and Embase up to 2/21/2018. Risk of bias was assessed with Cochrane Risk of bias tool. Fourteen RCTs with 1,462 generally healthy adults in need of endodontic treatment were included. 50% of the studies were at unclear risk and 50% at high risk of bias. Meta-analysis showed Visual Analog Scale (VAS) pain at 4–6 hours after Inferior Alveolar Nerve Block (IANB) was significantly lower by 21 points (0–100 scale) in the corticosteroid group compared to the control group (95% CI −35 to −7; P = 0.003), however this difference was not statistically significant after 24 hours (P = 0.116). The route of administration was oral and intraligament injection. Patients who received corticosteroids prior to IANB were 70.7% more likely to have none or mild pain 4–8 hours after treatment (P = 0.001) and 13.5% more likely 24 hours after IANB (P = 0.013) than patients in the control group. In conclusion, corticosteroid administration (oral or intraligamental) may clinically reduce the level of postoperative pain at 4–8 hours after IANB, however the quality of the evidence was low/moderate due to risk of bias and heterogeneity. Further studies are recommended.