The Danish Twin Registry (DTR) has for more than 50 years been based on surveys and clinical investigations and over the two last decades also on register linkage. Currently these two approaches are merged within Statistics Denmark. Here we report on three major groups of register-based research in the DTR that used the uniqueness of twinning. First, we focus on the ''long-term prognosis'' of being a twin compared with being a singleton and show that Danish twins have health trajectories in adulthood similar to singletons, which is a result of interest for twins and their families as well as a test of the fetal origins hypothesis that states that fetal growth restriction has long-term health consequences. Secondly, we summarise some of the most important register-based ''classical twin studies'', e.g. heritability studies on lifespan and exceptional longevity. Finally, we illustrate how the co-twin control method in a register setting can be used to control for the effect of rearing environment and genetic factors in studies of the association between exposures and health. The spectrum of register-based twin studies is very wide and have changed in accordance with methodological and data resource developments.