Objective: We recorded the data of patients performing Percutaneous Nephrolithotomy (PCNL) under combined spinal anesthesia with sedative mixtures of Ketamine-Propofol (KP) or Fentanyl-Propofol (FP). Background: The PCNL is usually done under General anesthesia (GA); combining spinal anesthesia with a mixture of sedative drugs has shown to provide an optimum intra and post-operative analgesic and sedative response without side effects. Patients and Methods: 100 healthy patients were enrolled for PCNL, after stabilization of the sensory block of spinal anesthesia patients were randomized into two groups; Group KP received 1 mg/Kg Ketamine and 1 mg/Kg Propofol diluted in 20 ml syringe given over 30 seconds and Group FP received 1 mic/Kg Fentanyl and 1 mg/Kg Propofol diluted in 20 ml syringe over 30 seconds; both groups will receive increment doses if the patient suffers from anxiety, pain or discomfort. Perioperative Hemodynamic data (HR, SBP, DBP, RR, and SpO2) were recorded; PACU stay time and post operative analgesia time were analyzed. Results: Sedative mixtures of FP and KP provided remarkably deep sedation levels for PCNL procedures under spinal anesthesia. Respiratory depression, hypotension and bradycardia were the major side effects reported in FP group which had mean decrease in RR of 4.63 breath/min (27.49%) with mean 3.77% drop in SpO2 levels. KP group produced significant increase in HR about 7 beats/min without reported side effects. Conclusion: Various sedation techniques may be applicable for PCNL procedures with routine premedication, mixtures of fentanyl-Propofol or Ketamine-Propofol could be used, and KP has advantages of stable hemodynamics, prolonged analgesic response intra and post-operatively with no appreciable side effects and more effective method of sedative mixture.