BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly encountered. It is associated with several comorbid diseases. However, its association with infectious biliary diseases is still unknown. Aims: We aimed to assess whether NAFLD is a risk factor for the development of acute cholangitis among patients with common bile duct (CBD) stones. Methods: We performed a retrospective study, including all patients with a documented diagnosis of CBD stone that had available data on the presence or absence of NAFLD. Descriptive analysis using uni-variate and multivariate models was used to assess whether an association existed between NAFLD and acute cholangitis. Results: We included 811 patients. Of them, 161 patients presented with acute cholangitis, vs. 650 patients who presented with symptomatic CBD stone without cholangitis. NAFLD was significantly more common in the cholangitis group compared to the non-cholangitis group (15.5% vs. 8.3%, p = 0.01). In univariate analysis, age (Odds ratio (OR) 1.04, p < 0.0001), male gender (OR 1.47, p = 0.03), hypertension (OR 1.81, p = 0.0008), hyperlipidemia (OR 1.59, p = 0.01), and NAFLD (OR 2.04, p = 0.006) were significantly associated with acute cholangitis. In multivariate analysis, NAFLD kept its association with acute cholangitis irrespective of age (OR 2.15, p = 0.005). Conclusions: NALFD showed a significant association with acute cholangitis among patients with a CBD stone. Clinicians should encourage treatment of NAFLD in general, and especially in the setting of gallstone disease.