© 2022 E. Efe Mercanoglu et al.This randomized prospective clinical study aimed to investigate the effects of dexmedetomidine or ketamine administration to total intravenous anesthesia (TIVA) on postoperative analgesia in subjects undergoing elective laparoscopic cholecystectomy procedures. 90 adults, American Society of Anesthesiologists (ASA) physical status 1 and II patients, who underwent elective laparoscopic cholecystectomy procedures were included in the study and randomized into three groups equally. Remifentanil, propofol, and rocuronium infusions were used for TIVA guided by the bispectral index. In group KETA, 10 μg/kg/min ketamine was added to TIVA before surgery, and in group DEX, 0.5 μg/kg/h dexmedetomidine was added to TIVA before surgery. Normal saline infusions were infused in the control group. Postoperative analgesia was provided with intravenous patient-controlled analgesia (PCA) morphine (1 mg bolus morphine, 5 min lockout time). Hemodynamic parameters, scores of visual analogue scale (VAS) for pain, rescue morphine requirements, and side effects such as sedation, nausea, and vomiting were recorded for 48 hours after surgery. Postoperative first analgesic requirement time was longer in group KETA (P<0.001), and it was longer in group DEX than in the control group (P<0.001). Pain scores were lower in group KETA and group DEX than in the control group at all corresponding times throughout the 48 h period of observation. Intravenous PCA morphine consumptions were higher in the control group than in group KETA (P<0.001 for all followed-up times), and they were higher in group DEX than in group KETA (P<0.001 for all followed-up times). It is concluded that the use of dexmedetomidine or ketamine infusions can be suitable as an additive for TIVA in the intraoperative period. Furthermore, the addition of both drugs to the TIVA protocol may improve postoperative pain relief and decrease opioid consumption.