Introduction The United Kingdom and World Health Organization recently changed their youth physical activity (PA) guidelines from 60 min of moderate- to vigorous-intensity PA (MVPA) every day, to an average of 60 min of MVPA per day, over a week. The changes are based on expert opinion due to insufficient evidence comparing health outcomes associated with different guideline definitions. This study used the International Children's Accelerometry Database to compare approaches to calculating youth PA compliance and associations with health indicators. Methods Cross-sectional accelerometer data (n = 21,612, 5-18 yr) were used to examine compliance with four guideline definitions: daily method (DM; ≥60 min MVPA every day), average method (AM; average of ≥60 min MVPA per day), AM5 (AM compliance and ≥5 min of vigorous PA [VPA] on ≥3 d), and AM15 (AM compliance and ≥15 min VPA on ≥3 d). Associations between compliance and health indicators were examined for all definitions. Results Compliance varied from 5.3% (DM) to 29.9% (AM). Associations between compliance and health indicators were similar for AM, AM5, and AM15. For example, compliance with AM, AM5, and AM15 was associated with a lower BMI z-score (statistics are coefficient [95% CI]): AM (-0.28 [-0.33 to -0.23]), AM5 (-0.28 [-0.33 to -0.23], and AM15 (-0.30 [-0.35 to -0.25]). Associations between compliance and health indicators for DM were similar/weaker, possibly reflecting fewer DM-compliant participants with health data and lower variability in exposure/outcome data. Conclusions Youth completing 60 min of MVPA every day do not experience superior health benefits to youth completing an average of 60 min of MVPA per day. Guidelines should encourage youth to achieve an average of 60 min of MVPA per day. Different guideline definitions affect inactivity prevalence estimates; this must be considered when analyzing data and comparing studies.