BACKGROUND: Methylprednisolone administered intravenously preoperatively has been shown to reduce pain, nausea, and fatigue after elective surgery. We aimed to show that 125 mg of methylprednisolone given intravenously 30 minutes before laparoscopic surgery for suspected appendicitis would reduce pain at rest during the first 3 postoperative days. METHODS: A multicenter, parallel-group, double-blind, placebo-controlled study was conducted including patients 18 years of age and older with an American Society of Anesthesiologist class of I–III undergoing laparoscopic surgery for suspected appendicitis. The primary outcome was pain at rest measured on the 11-point numerical rating scale 5 times during the first 3 days after surgery. The effect of 125 mg of methylprednisolone on postoperative pain at rest during the first 3 days was assessed using a mixed-effects model with time and intervention as main effects. RESULTS: From April 2016 to August 2016, 78 patients were included, and all were eligible for analysis of the primary outcome. The estimated effect of 125 mg of methylprednisolone on pain at rest during the first 3 days after surgery was a nonsignificant increase of 0.2 (95% confidence interval, -0.5 to 0.9; P = .571) on the 11-point numerical rating scale. There was no difference between the 2 groups regarding the need for opioid agonists during hospital stay on the first postoperative day (P = .381). CONCLUSIONS: A 125-mg dose of methylprednisolone given intravenously 30 minutes before laparoscopic surgery for appendicitis seemed no better than placebo at providing a clinical meaningful reduction in postoperative pain at rest. (Anesth Analg 2018;126:1712–20.