Common bile duct (CBD) stone is a commonly encountered disease that is associated with various clinical presentations ranging from the mild form of biliary colic to the severe complication of acute cholangitis. Recently, diabetes mellitus (DM) has been linked to the development of biliary diseases; however, no data regarding the association of DM with acute cholangitis development in the setting of CBD stone exist. The aim of the current study was to investigate whether DM represents a risk factor for acute cholangitis in patients with CBD stone. We performed a retrospective cross-sectional study from January 1, 2010 till June 1, 2020 of all patients presenting to Galilee Medical Center with various clinical presentations of documented CBD stone, including cholangitis, biliary pancreatitis, and biliary colic with abnormal liver enzymes. Overall, 687 patients were included in the final analysis. Among them, 101 patients (14.7%) had CBD stone associated with acute cholangitis (group A), as compared to 586 patients (85.3%) without acute cholangitis (group B). The average ages in groups A and B were 77.7 ± 13.6 and 62.5 ± 20.5 years, respectively (
P
< .0001). The prevalence of DM was significantly higher in group A as compared to group B (52.5% vs 36.3%,
P
= .001). On univariate analysis, age (odds ratio [OR] 1.05,
P
< .0001), male gender (OR 1.54,
P
= .04), and DM (OR 1.92,
P
= .002) were associated with acute cholangitis development, and on multivariate logistic regression analysis, the correlation was preserved for DM (OR 1.93, 95% confidence interval 1.26–2.96,
P
= .002). DM showed a significant association with acute cholangitis development among patients with CBD stone. Identification of bile duct stones in diabetic patients is of paramount importance since early diagnosis and treatment might prevent further life-threatening complications.