In this prospective, single-center study, a random forest (RF) model was used to determine factors influencing future physical and mental health-related quality of life (HRQoL) scores in older adults. Researchers analyzed N=3,124 older adults from the ESTHER cohort study (community-dwelling participants in Saarland, Germany) between 2008 and 2021. The analysis showed that the model’s prediction of physical HRQoL was reliable up to 6 years (R²=0.36) but was poor after that time point (R² ≤ 0.05). However, mental HRQoL could be predicted moderately well up to 12 years (R²≈0.20). Secondary analyses included feature importance ranking and partial dependence plots, as well as sex-specific subgroup testing. Additional results showed BPS healthcare needs, frailty, somatic symptom burden, and depressive/anxiety symptoms consistently ranked among the top predictors, with sex differences emerging at 12 years (women: BPS needs and morbidity, and men: depression and frailty). Some limitations are poor predictability of physical HRQoL beyond 6 years, omission of certain Patient Health Questionnaire (PHQ) items, and a single-country population sample. External validation was not performed, and the study did not include fairness checks for different subgroups.