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Purpose: To examine the prospective associations between body mass index (BMI) and health-related quality of life (HRQoL).Methods: Data were extracted from a longitudinal, nationally representative sample of 9916 men and women aged 18 years and over who were followed annually between 2006 and 2016 in the Household, Income and Labour Dynamics in Australia (HILDA) survey. HRQoL was assessed using the self-administered SF-36 questionnaire annually between 2006 (baseline) and 2016. BMI was calculated from self-reported height and weight and was classified into the following four categories of baseline BMI: underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥ 30 kg/m2). We used linear mixed-effects regression models to investigate the associations between change in BMI (kg/m2) and concurrent changes in HRQoL scores over 11 years.Results: BMI gain was associated with deterioration of Physical Component Summary (PCS) (P < 0.001), but not with change in Mental component summary (MCS) over the 11-year period. BMI gain was inversely associated (P < 0.001) with five of the eight HRQoL domains (physical functioning, role physical, bodily pain, general health and vitality) with a significant graded association according to baseline BMI category. Over the 11-year study period, every unit increase in PCS was associated with a decrease of 0.02 (P < 0.001), 0.03 (P < 0.001) and 0.04 (P < 0.001) BMI units per year among participants who were normal, overweight and obese at baseline, respectively. Five of the eight domains of HRQoL (physical functioning, role physical, bodily pain, general health and vitality) were inversely associated with BMI (P < 0.001) with a significant graded association according to baseline BMI category.Conclusions: Weight gain was not only associated with deterioration of HRQoL, and vice versa. The bi-directional association was stronger for physical than mental domains of HRQoL. [ABSTRACT FROM AUTHOR]