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Background: Although ultrasound-guided nerve blocks have lately been used to control pain, there is not much evidence assessing the outcome of trigeminal nerve block (TNB) in maxillofacial surgery. This study sought to evaluate the safety and efficacy of analgesia with an ultrasound-guided trigeminal nerve block (USGTNB) in patients undergoing unilateral maxillofacial surgery under general anesthesia. Methods: This single-blinded, parallel-group, randomized clinical trial included 50 adult patients who had American Society of Anesthesiologists physical status I or II and were prepared for elective unilateral maxillofacial procedure under general anesthesia. The patients were randomized into two groups. In the intervention (TNB) group, 25 patients received USGTNB using 5 ml of bupivacaine 0.25%, while in the control group, 25 patients received only general anesthesia. Total intraoperative fentanyl consumption was the primary outcome. The secondary outcomes were the intraoperative hemodynamic parameters besides the postoperative pain, total opioid consumption, complications, and patient satisfaction. Results: Compared to general anesthesia, USGTNB significantly reduced the intraoperative fentanyl consumption (2.38 ± 0.62 vs 0.36 ± 0.55, p < 0.001), and the intraoperative heart rate and mean arterial blood pressure at 1, 2, and 3 h (p < 0.001), the numerical rating score during the 24 postoperative hours (p < 0.001), and the postoperative nalbuphine consumption (11.60 ± 4.72 vs 1.92 ± 3.28, p < 0.001). USGTNB had a better safety profile and showed better patient satisfaction compared to general anesthesia alone (8.04 ± 0.89 vs 5.84 ± 0.90, p < 0.001). Conclusion: USGTNB can provide an effective, safe approach for controlling pain in adult patients undergoing maxillofacial surgery. [ABSTRACT FROM AUTHOR]