This study assesses the relationship between body mass index (BMI) and adult chronic diseases (diabetes mellitus type 2 [DM2], cardiovascular diseases [CVD] and cancers), in grandparents in the Lifeways Cross-Generation Cohort Study. BMI was either measured or reported, at baseline or 10-year follow-up, in 1,244 grandparents. Cumulative morbidity data were recorded at baseline, 3 and 10-year follow-up through questionnaires, General Practice note search, or both. Just over 42% of grandparents were overweight and 32.1% obese. In the multivariate analysis BMI showed a strong linear association with both DM2 (ptrend <0.001) and CVD (ptrend <0.001). There were no significant associations with cancers, but case numbers were small. Results were similar for waist circumference. This prospective study presents novel Irish data and confirms other recent Irish cross-sectional reports on adiposity and adult chronic disease, highlighting the need for effective health promotion interventions in older adults.