Background: Many studies have separately addressed the associations of informal caregiving with coresidence, a caregiver's work status, and health conditions, but not jointly. We examined how their parents' need for care affects middle-aged women's lifestyle and psychological distress, considering the potential simultaneity of decisions on caregiving and living adjustments.; Methods: We used 22,305 observations of 7037 female participants (aged 54-67 years) from a nationwide longitudinal survey in Japan conducted during 2009 and 2013. We considered the occurrence of parents' need for care (OPNC) as an external event and estimated regression models to explain how it affected the probabilities of the participants becoming caregivers, coresiding with parents, and working outside the home. We further conducted the mediation analysis to examine how the impact of OPNC on participants' psychological distress measured by Kessler 6 (K6) scores was mediated by caregiving and living adjustments.; Results: OPNC made 30.9% and 30.3% of middle-aged women begin informal caregiving for parents and parents-in-law, respectively, whereas the impact on residential arrangement with parents or work status was non-significant or rather limited. OPNC raised middle-aged women' K6 scores (range: 0-24) by 0.368 (SE: 0.061) and 0.465 (SE: 0.073) for parents and parents-in-law, respectively, and informal caregiving mediated those impacts by 37.7% (95% CI: 15.6-68.2%) and 44.0% (95% CI: 22.2-75.4%), respectively. By contrast, the mediating effect of residential arrangement with parents or work status was non-significant.; Conclusions: Results underscore the fact that OPNC tends to promote middle-aged women to begin informal caregiving and worsen their psychological distress.