Background: Practice guidelines for preoperative pain management recommend that multimodal analgesic therapy should be used for postsurgical patients. This method uses different analgesic agents, which may target different components of pain transmission to improve post-operative analgesia and decrease reliance on opiate-based medication. The practice of Multimodal analgesia includes the combined use of neuraxial blockage regional anesthesia and systemic medications and has been shown to reduce opioid use and side effects in surgical patients. However, the proportion of patients who receive this evidence-based approach is unknown. To assess the practice of multimodal analgesia among patients undergoing surgery under general anesthesia at Debere Markos Compressive Specialized Hospital, Northwest Ethiopia, 2022. Methods: After obtaining ethical approval a hospital-based cross-sectional study was conducted from February 22 to May 10, 2022, in Debere Markos Compressive specialized hospital. Data was collected, prospectively using questionnaires from anesthetists, nurses in the recovery room, and anesthesia record sheets. Patients were considered to have multimodal analgesia if they received two or more analgesics. Descriptive statistics were performed to identify the practice of multimodal analgesia. Results: A total of 200 participated in our study. We observed the practice of multimodal analgesia in patients who had undergone surgery under general anesthesia in the study period was 47%. Opiod is the most widely administered analgesia. It was given to 81.5% of patients. The practice of multimodal analgesia in emergency surgery was found to be 61.7%. During the study period, multimodal analgesia was more practiced among Bsc anesthetists and it was found to be 42.5%. The practice of multimodal analgesia in PACU was found to be 9%. Conclusion and Recommendation: The practice of multimodal analgesia for surgical patients in Debre Markos Specialized Compressive Hospital is underutilized. Anesthesia professionals should use a multimodal approach for preoperative pain management for all surgical patients. The Department of Anesthesia should develop a guideline for the treatment of perioperative pain.