Objective To investigate the clinical efficacy and safety of Danshu Capsule in the treatment of chronic cholecystitis and gallstones through a large-sample, multicenter, open-label real-world research. Methods A total of 9579 patients with chronic cholecystitis and/or gallstones who were treated in 329 hospitals of China from January 2017 to December 2019 were enrolled and divided into gallstones group with 1148 patients, chronic cholecystitis group with 5360 patients, and chronic cholecystitis+gallstones group with 3071 patients. All patients were treated with oral administration of Danshu Capsule at a frequency of 1-2 capsules/time, three times a day after meals, for 4 consecutive weeks. Abdominal pain, biliary dyspepsia, traditional Chinese medicine(TCM) syndromes, and imaging findings of the biliary system were recorded before and after treatment to evaluate the efficacy of medication, and adverse drug reactions were monitored to evaluate the safety of Danshu Capsule. The Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment, and the Wilcoxon rank-sum test was used for comparison between any two groups. The paired chi-square test was used for comparison of categorical data before and after treatment; the Kruskal-Wallis H method was used for comparison between multiple groups, and the Logistic regression analysis and the Nemenyi test was used for further comparison between two groups. Results After treatment with Danshu Capsule, all patients had significant reductions in the overall incidence rate of pain induced by lipid meal(χ~²=32.422, P<0.001), the frequency, duration, and degree of pain(Z=-1.985,-2.887, and-3.178, all P<0.05), the symptom scores of abdominal distension, abdominal fullness, belching, and nausea(all P<0.001), and the total symptom score of biliary dyspepsia(Z=-4.128, P<0.001) ; there were also significant reductions in the TCM syndrome scores of right upper quadrant pain, bitter taste, acid regurgitation, chest distress, abdominal distension, poor appetite, and heaviness of limbs(all P<0.05) and a significant reduction in total TCM syndrome score(Z=3.860, P<0.001) . Subgroup analysis showed that after treatment, the gallstones group, the chronic cholecystitis group, and the chronic cholecystitis+gallstones group had significant reductions in the degree, frequency, and duration of pain, the symptom score of biliary dyspepsia, and TCM syndrome score(all P<0.05), as well as a significant reduction in the number of patients with pain induced by lipid meal(P<0.001) . The chronic cholecystitis group had significantly greater reductions in the score of pain frequency, the score of pain duration, the score of pain degree compared with the other two groups(all P<0.05) . Ultrasound examination showed that after treatment, all patients had significant reductions in poor sound transmission of gallbladder, gallbladder wall thickness, incidence rate of gallbladder wall thickening or roughness, and the number and size of gallstones(all P<0.05) . Danshu Capsule showed an overall response rate of 74.75% in the treatment of gallbladder wall lesion and an overall response rate of 67.40% in the treatment of gallstones. A total of 84 patients reported adverse events, mainly gastrointestinal symptoms, and the overall incidence rate of adverse reactions was 0.87%. Conclusion Danshu Capsule can significantly alleviate the symptom of pain and improve the symptoms of biliary dyspepsia, TCM syndrome, and gallbladder imaging findings in patients with chronic cholecystitis and/or gallstones, with a low incidence rate of adverse reactions, and therefore, it is a safe and effective drug for the treatment of chronic cholecystitis and gallstones. [ABSTRACT FROM AUTHOR]