OBJECTIVE: Given a paucity of validity data for the EQ-5D in cancer patients, we investigated its psychometric properties and its ability to differentiate clinically different groups in patients with advanced NSCLC. METHODS: The EQ-5D index and Visual Analog Scale (VAS) were administered within a phase II trial of combination chemotherapy over 6 months (at baseline, start of each 3-week cycle, and end of patient's last cycle). Clinical assessments included radiological tumor response and Eastern Cooperative Oncology Group performance status (PS). Reliability was assessed using Cronbach's a (internal consistency) and Pearson correlation (test-retest). Analysis of variance assessed construct validity. Effect size (ES) and standardized response mean (SRM) were calculated to evaluate responsiveness to change in clinical indicators. RESULTS: Data from 195 patients were analyzed. Cronbach's a for EQ-5D index was 0.68 at baseline. Correlations for test-retest (mean=7 days between assessments) were 0.70 and 0.80 for the index and VAS, respectively. Index and VAS scores differentiated patients by PS at all assessments (p<0.05), demonstrating construct validity. Mean index scores were 0.73 (complete or partial response [CR/PR], n=42), 0.68 (stable disease [SD], n=90), and 0.58 (progressive disease [PD], n=32). Index scores were significantly lower in patients with PD, compared to those with CR/PR (p=0.047), while VAS scores showed no significant differences. ES and SRM for index change scores were: 1) -0.73 and -0.38, respectively, in patients whose PS worsened; -0.08 each in patients with stable PS at the beginning of cycle 6; and 2) -0.27 and -0.38, respectively, in patients with CR/PR; -0.36 and -0.34, respectively, in patients with SD; -0.44 and -0.28, respectively, in patients with PD. CONCLUSIONS: The EQ-5D was reliable and valid in NSCLC. EQ-5D scores differentiated patients by performance status and best tumor response, which is important for generating utilities associated with health states defined by these clinical indicators.