Objectives: The study aims to evaluate the efficacy of preemptive analgesia with Pregabalin on acute post-operative pain after open cardiac surgery. Methods: Patients who underwent elective cardiac surgeries were randomized into two groups. Group I (n=30) received 150 mg Pregabalin 1 h prior to induction of anesthesia, whereas group II (n=30) received placebo at the same time. All patients were received morphine PCA after extubation. Heart rates, blood pressure, respiratory rate, time to extubation, intensive care unit (ICU) stay duration, morphine consumption, pain score according to the visual analogue scale (VAS), sedation scores, and side effects were measured and recorded during 48 hours after extubation. Results: VAS scores at rest and during deep breath were lower in the group I (p<0.05). Morphine consumption for 24 and 48 h after extubation of the two groups were 15.37±2.94 mg, 30.87±5.05 mg and 21.53±4.17 mg, 42.13±7.00 mg, respectively, p<0.05. The incidence of vomiting and urinary retention was significantly lower in the group I compared with the group II (p<0.05). Conclusions: Premedication with Pregabalin provided a good preemptive analgesia after open cardiac surgery: decreased VAS scores at rest and during deep breath and lower morphine consumption for 48 postoperative hours.