© 2020 The Authors Background: Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population. Methods: This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (DLCO) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for DLCO and FVC; and the Composite Physiologic Index, based on % predicted values for DLCO, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score. Results: Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing DLCO (5.0 [4.0-6.1] per 10% decrease in % predicted). Conclusions: Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF. Trial Registry: ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov.