Importance: Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable. Objective: To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum. Data Sources: This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficile, Peptoclostridium difficile, Clostridioides difficile, CDF OR CDI OR c diff OR c difficile, Clostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitis, enterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence. Study Selection: Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years. Data Extraction and Synthesis: Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing. Results: A total of 95 studies with 19186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: β, -0.151, P =.001; North and South America vs Western Pacific: β, 0.136, P =.007), there was no difference by testing method (ie, culture vs polymerase chain reaction: β, 0.069, P =.052; culture vs enzyme immunoassay: β, -0.178, P =.051), income class (low-middle income vs high income: β, -0.144, P =.23; upper-middle vs high income: β, -0.020, P =.64), or period (before 1990 vs 2010-2020: β, -0.125, P =.19; 1990-1999 vs 2010-2020: β, -0.037, P =.42; 2000-2009 vs 2010-2020: β, -0.006, P =.86). Conclusions and Relevance: In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.