Background Surgical stress is one of the most common causes of perioperative anxiety and postoperative pain. Pregabalin and celecoxib (P/C) have different mechanisms of analgesia demonstrated after a variety of surgical procedures. This study was designed to evaluate the efficacy, sedation, and postoperative pain control using combination of P/C as against midazolam and celecoxib (M/C) as a premedication. Patients and methods Sixty adult patients (20-60 years of age), ASA physical status I and II, of either sex scheduled to undergo elective minor day-case surgeries were randomly allocated into two groups of 30 patients each in this prospective study. Group I (P/C) received oral pregabalin (150 mg) and celecoxib (200 mg) 1 h before surgery, whereas group II (M/C) received oral midazolam (7.5 mg) and celecoxib (200 mg) 1 h before surgery. Preoperative sedation level was assessed using the Ramsay sedation scale. Intraoperative and postoperative analgesic consumption, the time to first analgesic requirement, and postoperative pain were recorded using visual analog scale. Adverse events were also recorded. Results Preoperative sedation level and intraoperative hemodynamic parameters were significantly higher in the M/C group compared with the P/C group. Intraoperative and postoperative analgesic consumption were significantly higher in the M/C group, whereas the time for first analgesic requirement was significantly higher in the P/C group compared with the M/C group. Conclusion Premedication using combination of P/C in day-case surgery decreased analgesic consumption and had a good sedative level with limited adverse effects.