Objective: To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang\'an ⅠRecipe (肠安Ⅰ号方) in the treatment of irritable bowel syndrome with diarrhea (IBS-D). Method: A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatmentgroup or the placebo controlgroup, administrated with Chang\'an Ⅰ Recipe or placebo, 150mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests. Results: A total of 216 patients were included, with 109 in the treatmentgroup and 107 in the controlgroup, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6％ and 40.2％ for the treatment and controlgroups, respectively, with 95％ confidence interval (CI) for difference in the effective rates between the twogroups of 14.4％-40.2％; while in PPS, the total effective rate was 71.3％ and 41.2％ for the treatment and controlgroups, respectively (95％ CI 16.6％-43.4％). The consistent conclusions of FAS and PPS showed a better efficacy in the treatmentgroup. Both FAS and PPS showed higher AR responder in the treatmentgroup (FAS: 59.6％ vs. 35.5％; PPS: 62.8％ vs. 38.1％). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the twogroups (P＞0.05). Both anxiety and depression scales of HAD were not significantly different between the twogroups (P＞0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant. Conclusion: Chang\'an Ⅰ Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328)