Objective: To investigate effects of cold weather spells on incidence of cardiovascular disease (CVD), and potential effect modification of socio-demographic, clinical, behavioural and environmental exposures. / Methods: Data from two prospective studies were analysed: the British Regional Heart Study (BRHS), a population-based study of British men aged 60–79 years, followed for CVD incidence from 1998–2000 to 2012; and the PROSPER study of men and women aged 70–82 recruited to a trial of pravastatin vs placebo from 1997 to 9 (followed until 2009). Cold spells were defined as at least three consecutive days when daily mean temperature fell below the monthly 10th percentile specific to the closest local weather station. A time-stratified case-crossover approach was used to estimate associations between cold spells and CVD events. / Results: 921 of 4252 men from BRHS and 760 of 2519 participants from PROSPER suffered a first CVD event during follow-up. More CVD events were registered in winter in both studies. The risk ratio (RR) associated with cold spells was statistically significant in BRHS (RR = 1.86, 95% CI 1.30–2.65, p