The effect of overweight and obesity on the risk of fatal disease tends to attenuate with age. To evaluate whether this effect is partly attributable to disease-related weight loss, we examined the prebaseline history of weight loss and diseases associated with weight loss among adults enrolled in a cohort study. We conducted an analysis of 7,855 adult cohort members of the Adventist Health Study (AHS) I who had provided anthropometric data on surveys at baseline and 17 years prior to baseline. Among adults in the recommended range of BMI (19-25 kg/m(2)) at baseline we found that: (i) the prevalence of prebaseline weight loss of 5 kg/m(2) from an overweight or obese state was 20.4% and increased with age (12.6% for <65 years; 27.7% for 65-84 years; 36.7% for >85 years) and (ii) prebaseline weight loss of 5 kg/m(2) from an overweight or obese state was associated with diabetes (odds ratio (OR) = 2.91 95% confidence interval (CI) = (2.16, 3.93)), coronary heart disease (OR = 1.84 95% CI = (1.42, 2.40)), and high blood pressure (OR = 1.51 95% CI = (1.26, s1.82)). During 12 years of follow-up, we found evidence that hazard ratios for adiposity can be confounded by disease-related weight loss. Our findings raise the possibility that prebaseline weight loss can confound the estimation of risk due to adiposity at baseline in a cohort study.