The aims of this study were to: (i) assess the associations of the MTHFR C677T polymorphism with total stroke, including ischaemic stroke (IS) and intracerebral haemorrhage (ICH) types, and with ischaemic heart disease (IHD), including myocardial infarction (MI), and other IHD types after stratifying for the 10 study regions and adjusting for principal components; and (ii) examine the associations of the MTHFR C677T polymorphism with site-specific cancers and other diseases previously linked with low-folate status in a large prospective Chinese cohort study. Here, MTHFR is linked to ischemic stroke.