Objective: The purpose of the present study was to evaluate the natural course of primary degenerative sagittal imbalance (PDSI), its aggravating factors, and health-related quality of life (HRQoL) associated with various spinal alignment parameters (SAPs) in patients with PDSI who have not undergone surgery.Methods: One hundred three participants volunteered to participate. The SAPs, including T1 pelvic angle (T1PA), thoracolumbar tilt, and thoracolumbar slope (TLS), were measured on whole-spine standing radiographs. The back and lumbar muscle volumes were measured. To determine HRQoL at baseline and at 2-year follow-up, face-to-face questionnaires were administered, which included visual analogue scale of the back and leg, physical component summary/mental component summary of 36-item Short Form Health Survey, Oswestry Disability Index (ODI), and Mini-Mental State Examination.Results: Overall HRQoL measures had improved after 2 years of follow-up compared to baseline. PDSI aggravation was observed in 18 participants (26.1%). TLS, sagittal vertical axis (SVA), and T1PA were strongly correlated with each other. TLS, SVA, and T1PA were correlated with ODI score. Among them, TLS was most highly correlated with ODI score. TLS greater than -3.5° was a predicting factor for PDSI aggravation (p = 0.034; 95% confidence interval, 1.173–63.61; odds ratio, 8.636).Conclusion: The present study implied that PDSI does not necessarily worsen with aging. TLS is an appropriate parameter for assessing the clinical situation in patients with PDSI. Furthermore, a TLS greater than -3.5° predicts PDSI aggravation; thus, TLS may be a useful parameter for predicting prognosis in PDSI.