: Multimodal anesthesia represents a technique that can improve analgesia and lower the occurrence of opioid side effects in the postoperative period, such as postoperative nausea and vomiting (PONV). It can be achieved by providing different types of medication during the intraoperative period which can decrease the need for opioids. PONV happens more often in patients who have received large amounts of opioids during laparoscopic cholecystectomy. In this study, our aim was to observe the occurrence of PONV between three different groups of patients who received lidocaine, ketamine and magnesium sulfate in combination with fentanyl in the intraoperative period. We also observed any additional nausea and vomiting in the three groups as well as the amount of fentanyl given to these groups during operation. : 120 patients aged 20-65 years old were included in this randomized and prospective study, ASA classification 1 and 2, scheduled for laparoscopic cholecystectomy. Patients were classified into three groups randomly: Group 1 (lidocaine group-LG), these patients received lidocaine at 1 mg/kg during induction to general anesthesia and 2 mg/kg/h after intubation in continuous intravenous infusion; Group 2 (ketamine group-KG) these patients received ketamine at 0.5 mg/kg during induction to general anesthesia; and Group 3 (magnesium group-MG) these patients received magnesium sulfate at 1.5 gr/hr as a continuous intravenous infusion after intubation. In all three groups, patients additionally received bolus doses of fentanyl. Postoperative nausea and vomiting were monitored in all three groups at 1, 4, 8, 12, and 24 hours after surgery as a primary objective, and if patients had complainant of vomiting, they were treated with 10 mg of metoclopramid. Between the five control time points, additional nausea and vomiting was recorded as well, as a secondary objective. The third objective was to measure of the total amount of fentanyl given in the intraoperative period. : Patients from the lidocaine group experienced less PONV and they received less fentanyl compared to patients of ketamine and magnesium groups. Patients from the ketamine group had more nausea than other groups. In the magnesium group, the rate of vomiting was higher, and they received higher amounts of fentanyl during surgery. Additional nausea and vomiting occurred in 3 patients in the LG, 2 in the KG, and 3 in the MG between the five control time points. The patients from the magnesium group received the highest dose of fentanyl during surgery (307.50 ± 130.4), followed by the patients from the ketamine group (292.50 ± 60.5), and then patients from the lidocaine group (258.75 ± 60.9). The doses of fentanyl that patients received during surgery in all three groups were not statistically significant. : Multimodal anesthesia has been shown to lower PONV 24 hours after laparoscopic cholecystectomy and can lower need for opioids during laparoscopic cholecystectomy.