Objective To identify predictors of increased adiposity for different measures of adiposity. Design Prospective cohort study, the Melbourne Collaborative Cohort Study (MCCS), with data at baseline (1990-1994) and wave 2 (2003-2007). Setting Participants recruited from the community. Subjects Australian-born participants (n 5879) aged 40 to 69 years who were not current smokers and who were free from common chronic diseases at recruitment. At baseline and at wave 2, weight and waist circumference were measured; while demographic and lifestyle variables were obtained at baseline via structured interviews. Results Participants who reported any recreational physical activity at baseline had lower weight and smaller waist circumference at wave 2 than those who did not, particularly for younger participants and for vigorous physical activity. Walking for leisure was not associated, and greater physical activity at work was associated, with greater adiposity measures at wave 2. A diet low in carbohydrates and fibre, but high in fat and protein, predicted greater weight and waist circumference at wave 2. Participants were less likely to have elevated weight or waist circumference at wave 2 if they consumed low to moderate amounts of alcohol. Conclusions Our findings indicate that promoting vigorous physical activity, encouraging a diet high in carbohydrate and fibre but low in fat and protein, and limiting alcohol intake could be promising approaches for preventing obesity in middle-aged adults. Similar interventions should successfully address the management of both weight and waist circumference, as they were predicted by similar factors.