Background: Choledocholithiasis represents a significant hepatobiliary pathology with substantial morbidity and mortality worldwide. While traditional risk factors including age, sex, and obesity have been well-established, emerging evidence suggests that thyroid dysfunction—particularly hypothyroidism—may constitute an underrecognized etiological factor. Hypothyroidism influences multiple pathways affecting bile composition, gallbladder contractility, and sphincter of Oddi function, thereby predisposing to common bile duct (CBD) stone formation. Methods: A matched case-control study was conducted at a tertiary medical centre involving 70 consecutive patients with radiologically confirmed choledocholithiasis and 70 age- and sex-matched controls without biliary tract disease. Thyroid function tests (TSH, free T3, free T4), complete fasting lipid profiles, and anthropometric data were obtained for all participants. Chi-square analysis and independent t-tests were employed for statistical comparisons, with significance defined as p < 0.05. Results: Hypothyroidism was detected in 22.9% of CBD stone patients compared with 7.1% of controls (p = 0.009), yielding an odds ratio of 3.9. Mean TSH concentrations were significantly elevated in cases (3.6 ± 3.0 mIU/L) versus controls (2.6 ± 1.5 mIU/L, p < 0.05). Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were all significantly higher in the case group, whereas high-density lipoprotein cholesterol was lower (p < 0.01 for all). Mean T3 and T4 levels differed significantly between groups (p < 0.01 and p < 0.01, respectively), supporting the association between thyroid hormone deficiency and CBD stone pathogenesis. Conclusion: This study provides substantial evidence that hypothyroidism serves as an independent and statistically significant risk factor for choledocholithiasis, mediated through altered lipid metabolism, diminished bile flow, and impaired sphincter of Oddi relaxation. Routine thyroid function testing should be incorporated into the diagnostic workup of patients presenting with CBD stones, particularly those exceeding 50 years of age. These findings support a paradigm shift toward holistic endocrine assessment in hepatobiliary disease management