AbstractTobacco smoking is a well-established risk factor for cardiovascular disease, but its direct effect on myocardial structure and function remains unclear. This study investigated the effects of smoking using a nested matched case-control study design. 5,668 participants of the UK Biobank study who underwent cardiovascular magnetic resonance imaging were screened for inclusion. 102 smokers (56 males) with a median age of 56 years were matched to non-smokers based on sex, age, and body surface area. Manual post-processing and feature tracking analyses were performed to determine left ventricular (LV) and right ventricular (RV) structure and function measures. Linear regression analyses were performed to determine the effect of tobacco smoking on imaging measures. Tobacco smoking was associated with increased LV and RV end-systolic volume (4.98 ± 2.08 mL, 5.19 ± 2.62 mL, P = 0.018, 0.049 respectively), reduced LV and RV ejection fraction (β: −2.21 ± 0.82%, −2.06 ± 0.87%, P = 0.007, 0.019 respectively), and reduced absolute measures of LV peak global longitudinal, radial, and circumferential strain (β: 0.86 ± 0.30%, −2.52 ± 0.99%, 1.05 ± 0.32%, P = 0.004, 0.011, 0.001 respectively). Effect sizes were larger in daily smokers compared to occasional smokers. In a general Caucasian population without known clinical cardiovascular disease, active tobacco smoking was dose dependently associated with impaired cardiac systolic function.