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Background and Aims Persistent post-sternotomy pain is a disabling outcome of cardiac surgery, often under-recognized. While ESP blocks are increasingly used perioperatively, their role in preventing chronic pain—especially when combined with dexamethasone—has never been rigorously tested. Objective: To determine whether perineural dexamethasone with ESP block reduces long-term pain and functional impairment after CABG, using a structured 90-day follow-up.Methods Adult patients undergoing CABG were randomized to receive ESP blocks with ropivacaine ± dexamethasone (8 mg total). Pain intensity and interference were evaluated via the Brief Pain Inventory (BPI) at 30, 60, and 90 days. Evaluations included rest and movement conditions to capture the full pain spectrum.Results The dexamethasone group (n=22) demonstrated significantly lower pain scores at day 30 (worst pain: 1.77 vs. 2.24; p = 0.002) and less interference in key functions like sleep, activity, and enjoyment of life (global interference: 0.47 vs. 1.26; p = 0.023). These differences, most pronounced during movement, faded by day 90, when both groups reported minimal pain. No adverse events related to dexamethasone were observed.Conclusions This is the first randomized study to show that dexamethasone-enhanced ESP block reduces chronic post-sternotomy pain and its impact on daily life. By integrating movement-sensitive metrics and longitudinal follow-up, our findings underscore a novel, actionable strategy to prevent pain chronification in cardiac surgical patients. Future multicenter trials should build on this pioneering evidence.