Objectives: Mucopolysaccharidosis III, an autosomal recessive lysosomal storage disorder, is characterized by progressive mental retardation and behavioral problems. Meta-analysis of global mucopolysaccharidosis III epidemi-ology, which serves as a fundamental reference for public health decision-making, was not available prior to this study. To provide a systematic review and meta-analysis of birth prevalence of mucopolysaccharidosis III in multiple countries. Methods: MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of mucopolysaccharidosis III from inception until 1st July, 2020. A checklist adapted from STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) was used to assess the quality of all studies involved. Meta -analysis, adopting a random effects logistic model, was performed to estimate pooled birth prevalence of muco-polysaccharidosis III and its subtypes. Results: Twenty-five studies screened out of 1,826 records were included for data extraction. The pooled global mucopolysaccharidosis III birth prevalence was 0.76 cases (95% CI: 0.57-0.96) per 100,000 live births. The pooled global birth prevalence of mucopolysacchar-idosis III subtypes (A, B, and C) was 0.52 cases (95% CI: 0.33-0.72), 0.21 cases (95% CI: 0.12-0.30) and 0.01 cases (95% CI: 0.005-0.02) per 100,000 live births, respectively. Conclusions: Based on the global population size (7.8 billion) and the life span of patients, there would be 12-19 thousand mucopolysaccharidosis III patients worldwide. To our knowledge, this is the first compre-hensive systematic review that presented quantitative data fundamental for evidence-based public health decision-making by evaluating global epidemiology of mucopolysaccharidosis III.