Objective: To establish the prevalence of weight change in mid-aged women over a 2-year period, and to assess the relationship between weight change and physical and mental well-being (SF36) in order to begin debate about the need for quantified standards of weight gain. Design: Prospective study of weight change and well-being over a 2-year period among mid-aged women participating in a large national survey. Subjects: Seven thousand two hundred and seventy women without surgical menopause aged between 45 and 50 years (termed mid-aged), enrolled in the Australian Longitudinal Study on Women's Health. Measurements: Weight change (self-reported weight at two time points) and physical and mental well-being (SF-36) explored using linear regression, while adjusting for potential confounders. Results: Only half the women maintained their weight within 2.25 kg, and one-third gained more than this amount in a 2-year period. While weight gain (≥2.25 kg) was negatively associated with physical well-being, both weight loss and weight gain were associated with poorer mental well-being. Conclusion: This is the first prospective study using a large, population-based cohort to demonstrate that small changes in weight are associated with changes in well-being in mid-aged Australian women. It provides further evidence of the need for public health messages to specify the actual amount that constitutes weight gain, but further research is needed to establish these standards for the entire population.