Objectives Mid-life family caregivers (CGs) are at risk for participation restriction, which can worsen quality of care for care recipients (CR) and increase CG burden and poor health. We aimed to identify factors associated with participation restriction in mid-life CGs. Methods This was a cross-sectional study of CGs aged 40–64 years ( n = 1100) from the 2015 cohort of the National Study of Caregiving (NSOC)/National Health and Aging Trends Study (NHATS). Multivariate logistic regression was used to evaluate personal and caregiving attributes associated with restricted participation. Results Individual items from the negative and Positive aspects of caregiving (PAC) scales were associated with participation restriction. Mid-life caregivers with “frequent changes to caregiving routine” and “no time for self” were more likely to report restricted participation and those feeling “closer to the CR” were less likely to report restricted participation. Discussion Interventions to optimize caregiving routines and improve dyadic relationships could decrease participation restriction in mid-life CGs.