To compare HRQoL differences with CHD in generic indexes and a proxy CVD-specific score in a nationally representative sample of U.S. adults. The National Health Measurement Study, a cross-sectional random-digit-dialed telephone survey of adults aged 35–89, administered the EQ-5D, QWB-SA, HUI2, HUI3, SF-36v2™ (yielding PCS, MCS, and SF-6D), and HALex. Analyses compared 3,350 without CHD (group 1), 265 with CHD not taking chest pain medication (group 2), and 218 with CHD currently taking chest pain medication (group 3), with and without adjustment for demographic variables and comorbidities. Data on 154 patients from heart failure clinics were used to construct a proxy score utilizing generic items probing CVD symptoms. Mean scores differed between CHD groups for all indexes with and without adjustment (P < 0.0001 for all except MCS P = 0.018). Unadjusted group 3 versus 1 differences were about three times larger than for group 2 versus 1. Standardized differences for the proxy score were similar to those for generic indexes, and were about 1.0 for all except MCS for group 3 versus 1. Generic indexes capture differences in HRQoL in population-based studies of CHD similarly to a score constructed from questions probing CVD-specific symptoms.