OBJECT Regional cervical sagittal alignment (C2-7 sagittal vertical axis [SVA]) has been shown to correlate with health-related quality of life (HRQOL). The study objective was to examine the relationship between cervical and thoracolumbar alignment parameters with HRQOL among patients with operative and nonoperative adult thoracolumbar deformity. METHODS This is a multicenter prospective data collection of consecutive patients with adult thoracolumbar spinal deformity. Clinical measures of disability included the Oswestry Disability Index (ODI), Scoliosis Research Society-22 Patient Questionnaire (SRS-22), and 36-Item Short-Form Health Survey (SF-36). Cervical radiographic parameters were correlated with global sagittal parameters within the nonoperative and operative cohorts. A partial correlation analysis was performed controlling for C-7 SVA. The operative group was subanalyzed by the magnitude of global deformity (C-7 SVA ≥ 5 cm vs < 5 cm). RESULTS A total of 318 patients were included (186 operative and 132 nonoperative). The mean age was 55.4 ± 14.9 years. Operative patients had significantly worse baseline HRQOL and significantly larger C-7 SVA, pelvic tilt (PT), mismatch between pelvic incidence and lumbar lordosis (PI-LL), and C2-7 SVA. The operative patients with baseline C-7 SVA ≥ 5 cm had significantly larger C2-7 lordosis (CL), C2-7 SVA, C-7 SVA, PI-LL, and PT than patients with a normal C-7 SVA. For all patients, baseline C2-7 SVA and CL significantly correlated with baseline ODI, Physical Component Summary (PCS), SRS Activity domain, and SRS Appearance domain. Baseline C2-7 SVA also correlated with SRS Pain and SRS Total. For the operative patients with baseline C-7 SVA ≥ 5 cm, the 2-year C2-7 SVA significantly correlated with 2-year Mental Component Summary, SRS Mental, SRS Satisfaction, and decreases in ODI. Decreases in C2-7 SVA at 2 years significantly correlated with lower ODI at 2 years. Using partial correlations while controlling for C-7 SVA, the C2-7 SVA correlated significantly with baseline ODI (r = 0.211, p = 0.002), PCS (r = -0.178, p = 0.009), and SRS Activity (r = -0.145, p = 0.034) for the entire cohort. In the subset of operative patients with larger thoracolumbar deformities, the change in C2-7 SVA correlated with change in ODI (r = -0.311, p = 0.03). CONCLUSIONS Changes in cervical lordosis correlate to HRQOL improvements in thoracolumbar deformity patients at 2-year follow-up. Regional cervical sagittal parameters such as CL and C2-7 SVA are correlated with clinical measures of regional disability and health status in patients with adult thoracolumbar scoliosis. This effect may be direct or a reciprocal effect of the underlying global deformities on regional cervical alignment. However, the partial correlation analysis, controlling for the magnitude of the thoracolumbar deformity, suggests that there is a direct effect of cervical alignment on health measures. Improvements in regional cervical alignment postoperatively correlated positively with improved HRQOL.