Background: Interfascial plane block can be used to treat postoperative pain after laparoscopic surgery. This study aimed to investigate the effect of ultrasound-guided unilateral rhomboid intercostal and subserratus plane (RISS) block after laparoscopic cholecystectomy on the amount of analgesic consumption. Methods: Fifty patients who underwent laparoscopic cholecystectomy were included in this quasi-experimental study. Patients fulfilling the inclusion criteria were analyzed in two groups: RISS group (RISS block with 20 ml of 0.25% bupivacaine + intravenous patient-controlled analgesia [IV-PCA] tramadol [n = 25]); and Control group (IV-PCA tramadol [n = 25]). The primary outcome was the total amount of tramadol used over 24 h. Secondary outcomes included side effects, additional analgesic use, and postoperative pain (at rest and during activity) at 2, 6, 12, and 24 h according to numerical rating scale (NRS) scores. Results: Postoperative tramadol consumption at 24 h was significantly lower in the RISS group than in the Control group (P < 0.001). Resting NRS scores at 2 h and 6 h were significantly lower in the RISS group. NRS scores during movement in the RISS group were significantly lower at 2, 6, and 12 h postoperatively. There was no statistically significant difference in the rate of side effects and additional analgesic use between the groups (P > 0.05). Conclusions Unilateral RISS block was an effective method for pain management after laparoscopic cholecystectomy and can be used as a part of multimodal analgesia.