Background: Pain after surgery decreases the quality of life and has also been reported as being the main source of concern for cardiac surgery patients. It was stated that patients with higher anxiety and depression levels after operation have higher requirements of analgesics for postoperative pain. Reduction of pain and anxiety after cardiac surgery is valuable for the healing process and improvement of the overall experience. Objective: To determine if the multimodal regimen of dexamethasone, gabapentin, ibuprofen, ketorolac, and paracetamol was with less complications following open-cardiac surgeries compared to IV morphine. Patients and Methods: Sixty patients were scheduled for sternotomy elective open-heart surgeries. The patients were randomized to one of two groups (ratio 1:1) utilizing sealed envelopes by the study coordinator.30 patients in each group. This prospective, randomized, and a controlled clinical trial was performed at Sohag University Hospital. Results: Patients in the multimodal group suffered fewer major in-hospital complications than in the morphine group. Acute coronary syndrome had occurred in (one versus zero) patients with a percentage of (3.3%) in the morphine group. Cardiac tamponade had occurred in (two versus one) patients with a percentage of (6.7%) in the morphine group and was with a percentage of (3.3%) in the multimodal group with (p-value) of (0.554). The duration of hospital stays was with M± SD of (7±1.72) days among the multimodal group versus (11±1.6) days in the morphine group, with (a p-value) of (<0.001). Conclusions: Patients in the multimodal group suffered less major in-hospital complications than in the morphine group after cardiac surgeries.