Purpose: The primary objective was to use isotemporal substitution models to estimate whether replacing time spent in sedentary video games (SVGs) and active outdoor play (AOP) with active video games (AVGs) would be associated with changes in youth's mental health. Methods: A representative sample of 20,122 Canadian youth in Grades 6-10 was studied. The exposure variables were average hours/day spent playing AVGs, SVGs, and AOP. The outcomes consisted of a negative and internalizing mental health indicator (emotional problems), a positive and internalizing mental health indicator (life satisfaction), and a positive and externalizing mental health indicator (prosocial behavior). Isotemporal substitution models estimated the extent to which replacing time spent in SVGs and AOP with an equivalent amount of time in AVGs had on the mental health indicators. Results: Replacing 1 hour/day of SVGs with 1 hour/day of AVGs was associated with a 6% (95% confidence interval: 3%-9%) reduced probability of high emotional problems, a 4% (2%-7%) increased probability of high life satisfaction, and a 13% (9%-16%) increased probability of high prosocial behavior. Replacing 1 hour/day of AOP with 1 hour/day of AVGs was associated with a 7% (3%-11%) increased probability of high emotional problems, a 3% (1%-5%) reduced probability of high life satisfaction, and a 6% (2%-9%) reduced probability of high prosocial behavior. Conclusions: Replacing SVGs with AVGs was associated with more preferable mental health indicators. Conversely, replacing AOP with AVGs was associated with more deleterious mental health indicators. (C) 2016 Society for Adolescent Health and Medicine. All rights reserved.