Background and Aims Laparoscopic cholecystectomy (LC) is a common surgical method for the treatment of gallbladder diseases. However, some patients experience symptoms such as dyspepsia after surgery, which can affect their quality of life. Compound azinomide enteric-coated tablets, a novel drug, may improve dyspeptic symptoms after LC. This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods A multicenter, superior efficacy, open-label, parallel-controlled design was used. Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024. Patients were randomly assigned to either the observation or control groups using a random number table. The observation group received compound azinomide enteric-coated tablets, while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets. Both groups were treated for 4 weeks. The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment. Additionally, the incidence of adverse reactions and cost-effectiveness ratio (CER) were compared between the groups.Results A total of 303 patients were included, with 150 in the observation group and 153 in the control group. Baseline characteristics were balanced between the groups before treatment (all P>0.05). After treatment, the observation group showed significantly higher effective rates at 14 d and 28 d than the control group (44.7% vs. 29.4%; 98.0% vs. 73.9%, both P<0.05). The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d, with a significantly higher improvement rate in symptom scores compared to the control group (all P<0.05). Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that, except for the 14-d improvement in abdominal pain/discomfort, the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group (all P<0.05). No adverse reactions were observed in either group. The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d, while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness. Despite some limitations, the results provide a new treatment option for dyspepsia after LC. Larger-scale randomized controlled trials are needed to validate this study's conclusions further.