Study Design:Secondary analysis of prospective, multicenter data. Objective:To evaluate impact of sagittal parameters on health-related quality of life (HRQoL) in adults with lumbosacral spondylolisthesis. Methods:Adults with unoperated lumbosacral spondylolisthesis were identified in the Spinal Deformity Study Group database. Pearson's correlations were calculated between SF-12 (Short Form-12)/Scoliosis Research Society-30 (SRS-30) scores and radiographic parameters (C7 sagittal vertical axis [SVA] deviation, T1 pelvic angle, pelvic tilt [PT], pelvic incidence, sacral slope, slip angle, Meyerding slip grade, Labelle classification). Main effects linear regression models measured association between individual health status measures and individual radiographic predictor variables. Results:Forty-five patients were analyzed (male, 15; female, 30; average age 40.5 ± 18.7 years; 14 low-grade, 31 high-grade). For low-grade slips, SVA had strong negative correlations with SF-12 mental component score (MCS), SRS-30 appearance, mental, and satisfaction domains (r = -0.57, r = -0.60, r = -0.58, r = -0.53, respectively; P < .05). For high-grade slips, slip angle had a moderate negative correlation with SF-12 MCS (r = -0.36; P = .05) and SVA had strong negative correlations with SF-12 physical component score (PCS), SRS-30 appearance and activity domains (r = -0.48, r = -0.48, r = -0.45; P < .05) and a moderate negative correlation with SRS-30 total (r = -0.37; P < .05). T1 pelvic angle had a moderate negative correlation with SF-12 PCS and SRS-30 appearance (r = -0.37, r = -0.36; P ≤ .05). For every 1° increase in PT, there was a 0.04-point decrease in SRS appearance, 0.05-point decrease in SRS activity, 0.06-point decrease in SRS satisfaction, and 0.04-point decrease in SRS total score (P < .05). Conclusion:Lumbosacral spondylolisthesis in adults negatively affects HRQoL. Multiple radiographic sagittal parameters negatively affect HRQoLs for patients with low- and high-grade slips. Improvement of sagittal parameters is an important goal of surgery for adults with lumbosacral spondylolisthesis.