Background We aimed to investigate the relationship between potentially modifiable risk factors in middle age and disability after 13 years using the Framingham Offspring Study (FOS). We further aimed to develop a disability risk algorithm to estimate the risk of future disability for those aged 45?65 years. Methods FOS is a longitudinal study. We used examination 5 (1991?1995; `baseline?) and examination 8 (2005?2008; `follow-up?). We included participants aged between 45?65 years at `baseline? with complete predictor and outcome measures (n=2031; mean age 53.9 years). Predictors considered were body mass index, smoking, hypertension, diabetes and dyslipidaemia. We used multinomial logistic regression to identify predictors of disability or death.We assessed external validity using Australian data. Results By examination 8, 156 participants had disability and 198 had died. Disability was associated with smoking (OR (95 CI) 1.81 (1.18 to 2.78)); obesity (2.95 (1.83 to 4.77)); diabetes 1.96 (1.11 to 3.45) and being female (OR 1.67 (1.13 to 2.45). The model performed moderately well in predicting disability and death in an Australian population. Based on our algorithm, a 45-year-old man/woman with the combined risk factors of obesity, diabetes and smoking has similar likelihood of surviving free of disability to a 65-year-old man/woman without any of the same risk factors. Conclusions and relevance The derived risk algorithm allows, for the first time, quantification of the substantial combined impact on future disability of key modifiable risk factors in mid-life. Here we demonstrated the combined impact of obesity, diabetes and smoking to be similar to 20 years of aging.