BACKGROUND: We examined differences in cancer incidence between women and men and the extent to which these persisted after accounting for established risk factors. METHODS: Prospective analyses in the UK Biobank to examine associations between sex and risk of 15 cancers (and 13 subtypes) using minimal and multivariable-adjusted Cox proportional hazards regression models. Multivariable models were stratified for age, deprivation index, and region, and adjusted for ethnicity, qualifications, height, BMI, smoking status, alcohol, and site-specific risk factors. RESULTS: During 10.5 (SD 2.2) years of follow-up, 32,315 incident cancers across 15 anatomical sites (58.1% in women) were identified in 470,771 individuals (53.8% women). Some differences in cancer risk between the sexes attenuated to the null in the multivariable-adjusted models, but men remained at greater risk than women for cancers at eight sites: oesophageal adenocarcinoma (hazard ratio 5.45; 95% confidence interval, 4.18-7.12), gastric cardia (3.65; 2.48-5.38), bladder (3.47; 2.85-4.24), oral cavity (2.06; 1.69-2.51), liver (1.91; 1.48-2.47), kidney (1.77; 1.51-2.09), rectum (1.70; 1.47-1.96), and leukaemia (1.43; 1.21-1.69). Men had lower risks for cancers of the breast, thyroid (0.36; 0.26-0.49), anus (0.41; 0.26-0.64), and lung adenocarcinoma (0.72; 0.62-0.84). CONCLUSION: Further research on these sex differences in risk may provide insights into cancer aetiology.