BACKGROUND: Over the past few decades, many studies assessing the effect of thiazide diuretics showed controversial results. Additionally, recent guidelines fail to address the optimal dosage and treatment duration of thiazide diuretics. Therefore, we conducted a meta-analysis to evaluate the efficacy, optimal dosage, and treatment duration of thiazide diuretics in preventing recurrent urolithiasis. METHODS: We conducted a comprehensive search of three electronic databases (PubMed, Embase and Cochrane Library) up to January 2024, utilizing specific keywords to identify eligible studies. Subsequently, we performed an overall meta-analysis. Subgroup analysis was also performed to evaluate the efficacy, optimal dosage, and treatment duration of thiazide diuretics. RESULTS: Twelve eligible studies were included, with a total of 1217 patients. Overall, our findings demonstrated the efficacy of thiazide diuretics in preventing recurrent urolithiasis (RR = 0.55, 95% CI = 0.39 to 0.76). The Egger's test indicated that our analysis was free of publication bias (P = 0.092). In the dose-effect analysis, we observed that hydrochlorothiazide group using daily doses of 50 mg was statistically effective. Regarding the treatment duration, we found that treatment with all thiazide diuretics for ≤ 12 monthswas statistically insignificant, while treatment with all thiazide diuretics for 24 and 36 months was demonstrated to be effective. Treatment with hydrochlorothiazide for 36 months was also demonstrated to be effective. CONCLUSIONS: We demonstrated the efficacy of thiazide diuretics in preventing recurrent urolithiasis. For the optimal dosage and treatment duration, we recommend a daily dose of 50 mg of hydrochlorothiazide for 36 months.