In the search for opioid-free anesthesia, notable numbers of drugs, singly or in combinations, have been tested with variable results. However, most of the drugs used are not as strong as opioids. Even if some non-opioid drugs are potent enough, they cause significant untoward effects, necessitating the use of lower effective dosages of multiple drugs as a substitute. The present pilot study evaluated low-dose combinations of ketamine, lignocaine, and dexmedetomidine (KeLiDex) against fentanyl-based anesthesia for analgesia and recovery profiles in laparoscopic nephrectomies. Twenty patients (10 in each group) randomly received KeLiDex or fentanyl infusion as an analgesic component for balanced general anesthesia. Entire patients also received paracetamol and quadratus lumborum block-2. Anesthesia depth, neuromuscular blockade, and reversal were standardized. Intraoperative hemodynamic variation, time to extubation after reversal (T-tEAR) administration, postanesthesia care unit (PACU) discharge readiness assessed using modified Aldrete score, sedations using Richmond Agitation Sedation Scale, postoperative pain, and rescue analgesia consumptions were compared using different validated scales. P-value <0.05 was considered significant. The KeLiDex group had a significantly lower heart rate (HR) between 45-90 minutes and at the time of reversal. Mean arterial pressure (MAP) (mean ± standard deviation (SD)) differed significantly at only a 60-minute interval (KeLiDex group 80.90 ± 9.50 versus fentanyl group 92.60 ± 16.13 mmHg, p-value 0.041). The Friedman test for change in HR and MAP over time within each group was also insignificant. The mean ± SD of T-tEAR was 6.37 ± 2.13 in KeLiDex, and 8.18 ± 2.92 minutes in the fentanyl group, p-value 0.27. Sedation scores, Modified Alderette scores, pain scores, and rescue analgesic requirements were also comparable. KeLiDex could effectively control hemodynamics and pain both at rest and in movements in line with fentanyl-based anesthesia for laparoscopic nephrectomies. Further, recovery from the anesthesia, sedation, and PACU discharge readiness were similar.