Although perceived obligations to meet the expectations of family, friends, and society can be detrimental to physical health, much research in this area has thus far been conducted on Western samples. Research in cross-cultural psychology importantly suggests that positive health can be dependent on whether one engages in modes of being that are sanctioned by one’s culture. Specifically, cross-cultural research shows that better health is predicted when people from independence-prevalent cultures are able to exercise their personal autonomy and when people from interdependence-prevalent cultures are able to maintain relational harmony (Kitayama, Karasawa, Curhan, Ryff, & Markus, 2010). Based on these two lines of research, we posit that culture would moderate the health effects of perceived obligations since perceived obligations can be conducive to relational harmony but may infringe on personal autonomy. To gain further insight, we additionally examined people’s goal disengagement tendency as an individual difference that may influence their likelihood of shunning perceived obligations and avoiding associated stressors. Thus, we examined the interaction between perceived obligations and goal disengagement tendency on health as indexed by biomarkers of inflammation and cardiovascular risk among American and Japanese middle-aged adults. We found that a higher tendency to disengage from stressful social obligations is associated with better health for Americans but poorer health for the Japanese. Our moderated moderation result supports the hypothesis that culturally distinct pathways underlie health outcomes.