<p><b>BACKGROUND: </b>Although Hispanic/Latino youth experience a high burden of cardiometabolic risk factors, few studies address regional differences.</p><p><b>OBJECTIVE: </b>We assessed differences between urban areas in metabolic syndrome and cardiometabolic markers among US Hispanic/Latino youth and examined underlying factors explaining these differences.</p><p><b>METHODS: </b>Cross-sectional study of youth (n = 1466, aged 8-16 years) in four US urban areas (Chicago, Bronx, Miami and San Diego) of the Hispanic Community Children's Health Study/Study of Latinos. Metabolic syndrome was ascertained following the International Diabetes Federation criteria. Socio-demographics, perceived environmental characteristics and diet quality were collected through questionnaires. Physical activity was measured using accelerometry. Survey regression models assessed the association between urban areas and metabolic syndrome.</p><p><b>RESULTS: </b>There were differences across urban areas in socio-demographic, behavioural and perceived environmental characteristics. Relative to youth in the four urban areas, youth in Chicago (odds ratios [OR]: 2.39, 95% confidence interval [CI]: 1.29, 4.42), but not Bronx and San Diego, had higher odds of metabolic syndrome, while youth in Miami had lower odds of this syndrome (OR: 0.32, 95% CI: 0.12, 0.85).</p><p><b>CONCLUSION: </b>We found differences across US urban areas in metabolic syndrome in Hispanic/Latino youth. Although behavioural and environmental characteristics partially explained these differences, future research is needed to understand persistent differences.</p>