Nausea and vomiting, pruritus, and shivering are among the most common complications induced by the administration of intrathecal opioids after surgery. Considering that the interaction between opioids and 5-hydroxytryptamine type 3 (5-HT3) receptors can play a significant role in causing these complications, this study aimed at evaluating the effect of ondansetron as a 5-HT3 receptor antagonist on reducing the incidence of nausea and vomiting, pruritus, and shivering after intrathecal injection of fentanyl in orthopedic surgeries. The present triple-blind, randomized, controlled, clinical trial was conducted on 90 patients that were candidates for lower limb orthopedic surgeries. Thirty minutes after spinal anesthesia, 4 mg of ondansetron, 8 mg of ondansetron, and 4 CC of distilled water (as a placebo) were intravenously administered to the patients in the first, second, and third groups, respectively. During 4 hours after surgery, the incidence and severity of postoperative nausea and vomiting (PONV), pruritus, and shivering were recorded. The results of the present study revealed that the incidence of PONV, pruritus, and shivering in the control group with the values of 53.3%, 20%, and 43.3%, respectively was significantly higher than their incidence in the ondansetron-4mg group with the values of 23.3%, 6.7%, and 23.3%, respectively and ondansetron-8mg group with the values of 16.7%, 10%, and 20%, respectively (P-value<0.05). Moreover, the severity and incidence of these complications were not significantly different between the two ondansetron doses (P-value>0.05). According to the results of the present study, the preventive administration of ondansetron can significantly reduce the incidence of PONV, pruritus, and shivering after surgery; however, there was no significant difference in the administration of its various doses.