OBJECTIVES: Health valuation studies enhance economic evaluations of treatments by estimating the value of health-related quality of life (HRQOL). The Patient-Reported Outcomes Measurement Information System (PROMIS) includes a 29-item short-form HRQOL measure, the PROMIS-29. METHODS: To value PROMIS-29 responses on a quality-adjusted life-year scale, we conducted a national survey (N = 7557) using quota sampling based on the US 2010 Census. Based on 541 paired comparisons with over 350 responses each, pair-specific probabilities were incorporated into a weighted least-squared estimator. RESULTS: All losses in HRQOL influenced choice; however, respondents valued losses in physical function, anxiety, depression, sleep, and pain more than those in fatigue and social functioning. CONCLUSIONS: This article introduces a novel approach to valuing HRQOL for economic evaluations using paired comparisons and provides a tool to translate PROMIS-29 responses into quality-adjusted life-years.