Aim This study aimed to evaluate the effectiveness of oral pregabalin as a preventive supplement in managing postoperative pain in patients undergoing coronary artery bypass grafting (CABG) with a combination of general anesthesia and high thoracic epidural anesthesia. Material and methods This 18-month randomized controlled study at a tertiary hospital's anesthesiology department included 62 American Society of Anesthesiologists (ASA) II or III patients aged 35-75 with left ventricular ejection fraction >35%. Placebo (Group B, n = 31) or pregabalin (Group A, n = 31) was randomly allocated. Group A got 150 mg of pregabalin the night before surgery and 75 mg on postoperative days 0 and 1, whereas Group B received a placebo. Postoperative pain was evaluated using the Verbal Numerical Scale and Visual Analogue Scale, while sedation was assessed with the Ramsay Sedation Scale. Statistical analysis was performed using SPSS for Windows, Version 16.0 (Released 2007; SPSS Inc., Chicago). Results In this study, pregabalin significantly reduced postoperative pain on Day 0 and Day 1 (p < 0.001) compared to the placebo. The pregabalin group exhibited higher sedation scores on Day 0 (p < 0.001), but there were no significant differences on Day 1. Inotrope requirements were similar between both groups. Conclusions CABG patients' postoperative pain was greatly reduced by pregabalin without impacting sedation or inotrope needs. These data imply that pregabalin was a useful supplementary analgesic for CABG patients' multimodal pain treatment.