Background To investigate the prevalence of caregiving and its relationship with work, health and socio-economic circumstances in the Health and Employment After Fifty (HEAF) study. Methods The HEAF study comprises 8134 men and women aged 50–64 years recruited from 24 general practices. Socio-demographic, lifestyle and health characteristics and hours per week giving personal care were elicited by postal questionnaire. Objective clinical information about diagnoses/medications was retrieved from health records. Work-related and health risk factors for intense caring responsibilities (≥20 h/week vs. no hours) were explored using logistic regression with adjustment for age and social class. Results In all, 644 (17%) men and 1153 (26%) women reported caring responsibilities, of whom 93 and 199 were intense caregivers, who were more likely to be socio-economically disadvantaged; less likely to be working and, if combining caring with working (41 men and 90 women), more likely to be part-time/working shifts, than non-carers. Men caring ≥20 h/week were more likely to have COPD and to report musculoskeletal pain, poor/fair self-rated health, depression and sleep problems. Among working women, caring ≥20 h/week was associated with these same health outcomes and also with a doctor-diagnosed mental health problem or musculoskeletal pain in the previous year. Conclusions Caregiving is common and unequal in the HEAF cohort, with more high-intensity informal care provided by those with greater levels of socio-economic deprivation, which could affect their employment and health. Caregivers need support to lead long, healthy lives, rather than becoming care needers themselves. Employers and governments need to take caregiving into account and support it actively.