Background: Despite several decades of research, the relevance of body fat and body fat distribution to the risk of cardiovascular disease remains unclear. This thesis aims to investigate associations of body-mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with risk of first-onset cardiovascular disease under a range of different circumstances. Methods: This thesis used individual records from the Emerging Risk Factors Collaboration to calculate risk ratios, and measures of discrimination and reclassification. 118 prospective studies, involving 1,064,541 participants without known history of cardiovascular disease, had information on BMI at baseline examination. 58 of these studies, involving 221,934 participants, had additional information on waist and hip circumference at baseline examination. Serial measurements made in 42,300 participants from 12 studies with concomitant information on these adiposity measures enabled quantification of within-person variability in BMI, WC and WHR. Results: Cross-sectional analyses demonstrated that although the correlations of adiposity measures differed with one another, BMI, WC and WHR were similarly and importantly associated with mediating cardiovascular risk factors, such as blood pressure, fasting glucose and lipids. Within-person variability was lower in BMI (regression dilution ratio: 0.96) than in WC (0.88) and WHR (0.66). The variability of adiposity measures was not materially influenced by several characteristics, although the variability of WHR varied somewhat by sex, diabetes status and baseline WHR values. 1,064,541 individuals with information on BMI recorded 161,903 deaths or non-fatal cardiovascular outcomes during 15.0 million person-years of follow-up. In analyses adjusted for age, sex and smoking status, BMI had positive and nearly loge-linear associations with coronary heart disease and ischaemic stroke (except at BMI values below 20 kg/m2), which were largely explained by the intermediate risk factors noted above. The association between BMI and non-vascular mortality was curvilinear. Data on 221,934 individuals with complete information on weight, height, and waist and hip circumference (14,297 incident cardiovascular outcomes; 1.87 million person-years of follow-up) demonstrated that BMI, WC and WHR were substantially and similarly related to risk of coronary heart disease and ischaemic stroke. For cardiovascular risk prediction, additional information on BMI, WC or WHR to a prediction model containing conventional risk factors did not importantly improve risk discrimination, nor classification of participants to risk categories of predicted 10-year risk. Conclusions: BMI, WC and WHR are similarly associated with risk of cardiovascular disease, with much of the risk explained by intermediate risk factors. These clinical measures of adiposity do not importantly improve cardiovascular risk prediction when additional information is available on blood pressures, history of diabetes and lipids.