BACKGROUND: It is unclear if muscle strength, another index of fitness, which confers the protection from cardiometabolic risk in adults, is associated with similar protection in children and youth. The purpose of this study was to investigate the association between handgrip strength and cardiometabolic health in a large Canadian sample of children and youth. METHODS: We performed a cross-sectional analysis of the Canadian sample of children and youth aged 6 to 19 years (n = 1376) studied in the Canadian Health Measures Survey (cycles 1 and 2) between 2007 and 2011. The primary exposure variable, handgrip strength, was measured using a handgrip dynamometer. The primary outcome measure was a composite measure of cardiometabolic risk calculated as the sum of z-scores of the following variables: triglycerides, low high-density lipoprotein cholesterol, systolic and diastolic blood pressures, and hemoglobin A1c. All of the analyses were adjusted for confounders. RESULTS: The sample was on average 12.8 ± 3.5 years and displayed a body mass index (BMI) z-score of 0.5 ± 1.2. In unadjusted analyses, handgrip strength was negatively associated with cardiometabolic z-score (estimate = -0.013; P < 0.001). When results were adjusted for age, BMI z-score, and cardiorespiratory fitness, the association was no longer significant; however, an interaction between handgrip strength, sex, and cardiometabolic z-score was observed (estimate = -0.042; P < 0.001). When analyses were stratified by sex, handgrip strength was negatively associated with cardiometabolic z-score (estimate = -0.038; P < 0.001) in girls, but not in boys (estimate = 0.008; P = 0.150). CONCLUSION: In a large sample of Canadian children and adolescents, handgrip strength was associated with cardiometabolic health in girls, but not in boys.