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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 exclusively on Western samples. Cross-cultural research importantly suggests that positive health can be dependent on whether one engages in modes of being that are sanctioned by one's culture. Specifically, studies show that better health is predicted when people from cultures that value independence are able to exercise their personal autonomy and when people from cultures that value interdependence are able to maintain relational harmony (Kitayama et al., 2010). Based on these lines of research, as the fulfillment of perceived obligations can facilitate relational harmony but infringe on personal autonomy, we posit that culture will moderate the impact of perceived obligations on health outcomes. 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 in order to avoid associated stressors. Drawing from the parallel biomarker projects of Midlife in the United States and Midlife in Japan, we examined the interaction between perceived obligations and goal disengagement tendency on health among American and Japanese middle-aged adults. Health outcomes were indexed by biomarkers of inflammation (interleukin-6 and C-reactive protein levels) and cardiovascular risk (systolic blood pressure and total/high-density lipoprotein cholesterol). We found that a higher tendency to disengage from stressful social obligations is associated with better health for Americans. In contrast, we found poorer health outcomes amongst Japanese participants who tend to disengage from their perceived obligations. Our results highlight the importance of examining how perceived obligations influence physical health from a cultural perspective. The current study supports the hypothesis that culturally distinct pathways underlie health outcomes. • Perceived obligations and biological health risks' associations differ by culture. • Disengaging from stressful obligations is linked to better health for Americans. • Disengaging from stressful obligations is linked to poorer health for the Japanese. • Results reveal culturally distinct pathways underlying health outcomes. [ABSTRACT FROM AUTHOR]