Background and aim <p>The negative impact of postoperative pain on various aspects of patients’ lives is evident, leading to the inability to perform daily activities and the inability to quickly return to normal function. The use of medications that can reduce pain and accelerate the healing process for patients. Therefore, the purpose of this study was to determine the effect of preoperative administration of oral montelukast on pain following surgery for zygomaticomaxillary complex fractures.</p> Methods <p>The present study was a triple-blind, randomized, controlled trial (Trial registration number: IR.TBZMED.DENTISTRY.REC.1403.043) that investigated 80 patients undergoing surgery for complex zygomaticomaxillary fractures who were randomly divided into two intervention and control groups. For each subgroup, 10 volunteers were used in each test (in each test, the drug montelukast was administered at different times: 0, 6, 12, and 24 h before the zygomaticomaxillary complex fracture surgery). The duration of surgery was also examined as a variable in this study and its effect on pain intensity was also examined. The collected data were analyzed using SPSS software. Different time intervals of drug administration before surgery, 6, 12 and 24 h and the effect of time of administration on pain intensity, the effect of surgery duration on pain intensity in the study groups were measured. Pain intensity was scored from 0 to 10 based on visual analog scale and verbal confession of the patient.</p> Results <p>Based on the results of an independent t-test, the mean pain score in patients receiving montelukast 6 h before surgery was significantly reduced compared to the control group at one, three, six, twelve, eighteen, and 24 h after surgery (<i>p</i> &lt; 0.05). In the intervention group that received montelukast 24 h before surgery, the lowest mean pain scores were observed one hour after surgery and the highest mean pain scores were observed eighteen hours after surgery in the intervention group (<i>p</i> &lt; 0.05). Based on the results of an independent t-test, the mean pain score in patients receiving montelukast before surgery was significantly reduced compared to the control group at three, six, twelve, eighteen, and 24 h (<i>p</i> &lt; 0.05).</p> Conclusion <p>Preoperative administration of montelukast significantly reduces postoperative pain following zygomaticomaxillary complex fracture surgery, with maximal efficacy when given six hours before surgery.</p>