Background: The association between change in weight or body mass index, and mortality is widely reported, however, both measures fail to account for fat distribution. Change in waist circumference, a measure of central adiposity, in relation to mortality has not been studied extensively. Methods: We investigated the association between mortality and changes in directly measured waist circumference, hips circumference and weight from baseline (1990-1994) to wave 2 (2003-2007) in a prospective cohort study of people aged 40-69 years at baseline. Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for confounding variables, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for change in body size in relation to mortality from all causes, cardiovascular disease and cancer. Results: There were 1465 deaths (109 cancer, 242 cardiovascular disease) identified during an average 7.7 years of follow-up from 21 298 participants. Compared to minimal increase in body size, loss of waist circumference (HR: 1.26; 95% CI: 1.09-1.47), weight (1.80; 1.54-2.11), or hips circumference (1.35; 1.15-1.57) were associated with an increased risk of all-cause mortality, particularly for older adults. Weight loss was associated with cardiovascular disease mortality (2.40; 1.57-3.65) but change in body size was not associated with obesity-related cancer mortality. Conclusion: This study confirms the association between weight loss and increased mortality from all-causes for older adults. Based on evidence from observational cohort studies, weight stability may be the recommended option for most adults, especially older adults. © 2014 Karahalios et al.