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Purpose: Most studies regarding the association of obesity with health-related quality of life (HRQoL) have assessed obesity at only one or two time points. We aimed to examine the associations of life course body mass index (BMI) from childhood with health-related quality of life (HRQoL) in mid-adulthood., Methods: Data were from a cohort study of Australian children (n = 2254, mean baseline age 12.0 (2.0) years in 1985, 46.8% male). Weight and height were measured at baseline and measured or self-reported on average 20, 25, and 30 years later. Age and sex-standardised BMI-z score was calculated at each time point. Physical and mental HRQoL and health state utilities (HSUs) were measured by SF-12 and SF-6D at the last adult follow-up. Linear regression was used to examine the associations adjusting for age, sex, and childhood health status., Results: Higher BMI-z score in childhood (β adjusted - 1.39, 95% CI - 1.73 to - 1.05) and increasing BMI-z score from childhood to young adulthood (β adjusted - 1.82, 95% CI - 2.17 to - 1.46) and from young to mid-adulthood (β adjusted - 1.77, 95% CI - 2.28 to - 1.26) were associated with lower physical HRQoL in mid-adulthood. Similar results were found for mid-adulthood HSUs (β adjusted ranged - 0.006 to - 0.014, all P < 0.05). Only increasing BMI-z score from young to mid-adulthood significantly related to poorer mental HRQoL (β adjusted - 0.74, 95% CI - 1.29 to - 0.19) in mid-adulthood., Conclusion: High BMI from childhood to mid-adulthood had only modest associations with HRQoL and HSUs, with effects on physical HRQoL most apparent., (© 2023. The Author(s).)