To investigate whether the relationship between the acute-chronic workload ratio (ACWR) and health problems varies when different methodological approaches are used to quantify it. Prospective cohort study. An online questionnaire was used to collect daily health and training information from 86 elite youth footballers for 105 days. The relationship between players' training load and health was analyzed using a range of different definitions of ACWR and health problems. We used 21-day and 28-day chronic periods, coupled and uncoupled calculations, and the exponentially weighted moving average and rolling average. Acute-chronic workload ratio data were categorized as low, medium, or high, using predefined categories and z scores. We compared medium to high, medium to low, and low to high categories. The outcome was defined in 3 ways: "all health problems," "all injuries," and "new noncontact injuries." We performed random-effects logistic regression analyses of all combinations, for a total of 108 analyses. We recorded 6250 athlete-days and 196 health problems. Of the 108 analyses performed, 23 (21%) identified a statistically significant (P<.05) association between the ACWR and health problems. A greater proportion of significant associations were identified when using an exponentially weighted moving average (44% of analyses), when comparing low to high categories (33%), and when using the "all health problems" definition (33%). The relationship between the ACWR and health problems was dependent on methodological approach. J Orthop Sports Phys Ther 2021;51(4):162-173. Epub 20 Jan 2021. doi:10.2519/jospt.2021.9893.