Background: Pain is one of the most challenging issues following surgery, and it is crucial to provide adequate and appropriate pain control measures. Objectives: This study assessed the efficacy of preoperative duloxetine in controlling postoperative pain in women following an abdominal hysterectomy in Yas Hospital affiliated to Tehran University of Medical Sciences between December 2019 and April 2020. Methods: The study involved 80 women who were candidates for elective abdominal hysterectomy. The participants were randomly assigned to one of two groups. Group 1 received a 60 mg duloxetine capsule two hours before surgery. Group 2 received placebo following the same schedule. The amount of administrated opioids and the time from surgery to the administration of opioids were recorded, along with the frequency of nausea and vomiting experienced. Results: Two patients from each group withdrew before the study ended. In total, 38 women in each group were assessed. There were no significant differences in age, duration of surgery, and the amount of administrated opioids between the two groups. However, the number of patients who had nausea and vomiting differed significantly between the two groups (65% vs. 34%; P = 0.006). Conclusions: Our findings showed that duloxetine was not effective in controlling pain after abdominal hysterectomy. In addition, patients who received duloxetine had a significantly higher rate of nausea/vomiting.