Background: Retrograde intrarenal surgery (RIRS) is a safe and minimally invasive method for the endoscopic treatment of upper urinary system stones especially sized <2 cm. Ureteral entrance is an important stage of RIRS. General anesthesia (GA) is usually used for RIRS. There is not enough data about the effect of anesthesia methods on the success of ureteral entrance and RIRS. We aimed to evaluate the effects of anesthesia methods (spinal anesthesia [SA], epidural anesthesia [EA], and GA) on the ureteral access and RIRS outcomes in primary surgery. Methods: After local ethical approval, 105 patients were prospectively randomized into three groups according to the anesthesia methods. GA, SA, and EA were defined as Group 1, 2, and 3, respectively. Results: Stone density was statistically significantly different between three groups (P = .008). Lithotripsy and operation time were significantly lower in Group 3 (P = .001). Dilatation and stone access time were significantly lower in Group 1. There was no statistically significant difference for scopy time, success, Visual Analog Scale score at 8th and 24th hours, and intraoperative and postoperative complications. Conclusions: GA may be recommended to decrease manipulations for the success of first ureteral access and time to reach the stone if there is not any contraindication.