OBJECTIVE: To investigate the associations between using alternatives to the car which are more active for commuting and non-commuting purposes, and morbidity and mortality. METHODS: We conducted a prospective study using data from 3 58 799 participants, aged 37-73 years, from UK Biobank. Commute and non-commute travel were assessed at baseline in 2006-2010. We classified participants according to whether they relied exclusively on the car or used alternative modes of transport that were more active at least some of the time. The main outcome measures were incident cardiovascular disease (CVD) and cancer, and CVD, cancer and all-cause mortality. We excluded events in the first 2 years and conducted analyses separately for those who regularly commuted and those who did not. RESULTS: In maximally adjusted models, regular commuters with more active patterns of travel on the commute had a lower risk of incident (HR 0.89, 95% CI 0.79 to 1.00) and fatal (HR 0.70, 95% CI 0.51 to 0.95) CVD. Those regular commuters who also had more active patterns of non-commute travel had an even lower risk of fatal CVD (HR 0.57, 95% CI 0.39 to 0.85). Among those who were not regular commuters, more active patterns of travel were associated with a lower risk of all-cause mortality (HR 0.92, 95% CI 0.86 to 0.99). CONCLUSIONS: More active patterns of travel were associated with a reduced risk of incident and fatal CVD and all-cause mortality in adults. This is an important message for clinicians advising people about how to be physically active and reduce their risk of disease.