Objective To investigate the dose-response associations of dietary inflammatory potential with all-cause mortality and incident cardiovascular disease (CVD) and cancer. Methods This was a prospective cohort study of 198,265 UK Biobank participants who completed at least 1 dietary assessment. A web based 24 hours recall questionnaire was used to derive the energy-adjusted dietary inflammatory index (E-DII). All-cause mortality and incident CVD and cancer ascertained from linked records. Results After adjusting for socio-demographic and lifestyle factors, there were J-shaped associations of E-DII with all-cause mortality and CVD, and a relatively linear association with cancer. When E-DII was <0, E-DII was not associated with any of the outcomes. When E-DII was ≥0, the linear associations were strongest in all-cause mortality (HR 1.09, 95% CI, 1.05-1.13), followed by CVD (HR 1.06, 95% CI, 1.03-1.09), and cancer (HR 1.03, 95%,CI, 1.01-1.05). Conclusion Dietary inflammatory potential was associated with mortality and CVD primarily when the diet is proinflammatory.