Here, we investigated if there are associations of ORAI1 polymorphisms with human cardiovascular disease.<h4>Methods and results</h4>We conducted candidate gene association analysis and revealed that a missense ORAI1 variant (rs3741596, S218G) associates with an increased risk of hospital-diagnosed peripheral vascular disease, generalised atherosclerosis, acute ischaemic heart disease, and atrioventricular and left bundle-branch block in White British UK Biobank participants. This evidence concerns the gene ORAI1 and vascular disorder.