This study examined both risk factors for the onset of work-family conflict and consequences in terms of need for recovery and prolonged fatigue for men and women separately. Two-year follow-up data from the Maastricht Cohort Study on "Fatigue at Work" (n = 12,095) were used. At baseline, the prevalence of work-family conflict was 10.8% (9.0% in women; 11.1% in men), the cumulative incidence at 1 year follow-up was 5.1%. For men, several work-related demands, shift work, job insecurity, conflicts with coworkers or supervisor, having full responsibility for housekeeping, and having to care for a chronically ill child or other family member at home were risk factors for the onset of work-family conflict, whereas decision latitude and coworker and supervisor social support protected against work-family conflict. In women, physical demands, overtime work, commuting time to work, and having dependent children were risk factors for work-family conflict, whereas domestic help protected against work-family conflict at 1 year follow-up. Work-family conflict was further shown to be a strong risk factor for the onset of elevated need for recovery from work and fatigue.