ABSTRACT: Cirrhosis is associated with disabling symptoms and diminished health-related quality of life (HRQOL). However, for patients with compensated disease, data are limited regarding associations with poor patient-reported outcomes (PROs). We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy (HE) and reviewed medical and pharmacy records. We characterized determinants of PROs using the 8-item Short-Form Health Survey (SF-8) scale (0-100) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI; poor sleep >5). Disability and frailty measures were assessed using activities of daily living (ADLs), falls, hand-grip, and chair-stands. Cognitive function was measured using weighted-lures from the Inhibitory Control Test (ICT). The median age of our cohort was 60 (interquartile range [IQR], 52-66) years, 56.3% were male, and 70% Child class A. All patients had portal hypertension, 76% had varices, and 41% had a history of ascites (predominantly well controlled). The median Model for End-Stage Liver Disease with Sodium (MELD-Na) score was 9 (IQR, 7-13). The overall median SF-8 was 70 (IQR, 54-86). Multivariate analysis showed that after adjusting for age, sex, education, and MELD-Na, performance on chair-stands (9.28 HRQOL points [95% confidence interval {CI}, 4.76-13.8] per 10-stands), ADL dependence (-6.06 [-10.8 to -1.36]), opiate use (-5.01 [-7.84 to -2.19]), benzodiazepine use (-3.50 [-6.58 to -0.42]), and ICT performance (-0.10 [-0.20 to 0.001] per weighted-lure) were significantly associated with HRQOL. Among patients completing the ICT, poor HRQOL (score <50) was significantly associated with chair-stands (odds ratio [OR] per 10-stands, 0.24; 95% CI [0.11-0.56]) and weighted lures (OR per weighted-lure, 1.01 [1.00-1.03]). Poor sleep quality was associated with opiate use (OR, 2.85 [1.11-7.29]) and lures (OR per-lure, 1.03 [1.00-1.05]). Conclusion: Disability, chair-stand performance, cognitive dysfunction, as well as psychoactive medication use are significantly associated with PROs in patients with clinically stable cirrhosis.