Studies on the association between shift-work and cardiovascular disease (CVD), in particular coronary heart disease (CHD), have given conflicting results. In this prospective population-based study we assessed the association of shift-work with three endpoints: CHD mortality, disability retirement due to CVD, and incident hypertension. A cohort of 20,142 adults (the Finnish Twin Cohort) was followed from 1982 to 2003. Type of working time (daytime/nighttime/shift-work) was assessed by questionnaires in 1975 (response rate 89%) and in 1981 (84%). Causes of death, information on disability retirement and hypertension medication were obtained from nationwide official registers. Cox proportional hazard models were used to obtain hazard ratios (HR) for each endpoint by type of working time. Adjustments were made for 14 socio-demographic and lifestyle covariates. 76.9% were daytime workers and 9.5% shift-workers both in 1975 and in 1981. During the follow-up, 857 deaths due to CHD, 721 disability retirements due to CVD, and 2,642 new cases of medicated hypertension were observed. However, HRs for shift-work were not significant (mortality HR men 1.09 and women 1.22; retirement 1.15 and 0.96; hypertension 1.15 and 0.98, respectively). The results were essentially similar after full adjustments for all covariates. Within twin pairs, no association between shift work and outcome was observed. Our results do not support an association between shift-work and cardiovascular morbidity.