Objective:To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒,TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D).Methods:A randomized,double-blind,double-dummy,and positive parallel controlled clinical trial was conducted from October 2014 to March 2016.Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1∶1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table.The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time),3 times per day.The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time),3 times per day.The treatment course lasted for 6 weeks.The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome.Secondary outcomes included adequate relief (AR) rate,Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL),Hamilton Anxiety Scale (HAMA),Hamilton Depression Scale (HAMD),and the recurrence rate at follow-ups.Safety indices including the adverse events (AEs) and related laboratory tests were evaluated.Results:Primary outcome:IBS-SSS at baseline,weeks 2,4,6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS,P＞0.05).After 6 weeks of treatment,the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0％)was higher than the control group (143/171,83.6％) by FAS (P＞0.05).In regard to secondary outcomes,after 6-week treatment,there was no significant difference in AR rate,total score of IBS-QOL,improvement of HAMD and HAMA total scores between the two groups (P＞0.05).The recurrence rate at 8-week follow-up was 12.35％ (10/18) in treatment group and 15.79％ (12/76)in control group,respectivery (P＞0.05).A total of 21 AEs occurred in 15 cases,of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group.The incidence of AEs had no statistical significance between the two goups (P＞0.05).Conclusion:Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide.(No.ChiCTR-IPR-15006415)