Background: Common bile duct (CBD) stones remain a significant surgical challenge, especially in patients with multiple calculi unresponsive to endoscopic extraction. Objective: To evaluate and compare early postoperative outcomes between open choledocholithotomy with T-tube drainage and choledochoduodenostomy in patients with multiple CBD stones. Methods: A quasi-experimental study was conducted from July 2022 to June 2024 at Rajshahi Medical College Hospital on 60 patients equally divided into two groups. Variables assessed included operative time, biochemical parameters, complication rates, and duration of hospitalstay. Statistical analyses were performed using SPSS v.26, applying t-tests and Chi-square tests where appropriate.Continuous data were expressed as mean ± SD; p < 0.05 was considered significant. Results: The mean operative timewas longer in the choledochoduodenostomy group (124.33 ± 3.59 min) than choledocholithotomy (103.67 ± 4.99 min; p = 0.03). Postoperative hospital stay was significantly shorter in CDD (7.05 ± 1.78 days) versus T-tube drainage (13.2 ± 2.11 days; p = 0.03). Serum bilirubin normalized faster in CDD (4.3 ± 1.33 mg/dL) than OCL (4.5 ± 1.41 mg/dL; p = 0.57). Alkaline phosphatase was lower (145.2 ± 4.45 IU/L vs. 153.4 ± 8.69 IU/L; p = 0.08). Wound infection occurred in 16.7% (CDD) vs. 26.7% (OCL; p = 0.35). Retained stones were significantly fewer in CDD (6.7%) than OCL (10.0%; p = 0.04). Mean postoperative leukocyte count decreasedmore rapidly in CDD (8.6 ± 1.12 × 10⁹/L) vs. OCL (10.1 ± 1.25 × 10⁹/L; p = 0.02), with lower CRP values (5.3 ± 0.91 mg/L s. 6.8 ± 1.14 mg/L; p = 0.01). Conclusion: Choledochoduodenostomy yielded significantly improved early postoperative recovery, lower inflammatory response, and reduced complications, making it a superior alternative for multiple CBD stone management.