OBJECTIVES: The purpose of this validation study was to test the accuracy and acceptability of an Internet-based questionnaire (Qx) assessing health-related quality of life (HRQoL) among subjects in CaPSURE, a longitudinal study of health outcomes among men with prostate cancer. METHODS: Active participants were sent a flyer with their usual bi-annual Qx offering the opportunity to test the new Internet version and were paid $25 for their participation. Volunteers were randomized to one of two Qx administration groups (paper-then-Internet or Internet-then-paper). The SF-36 and the UCLA Prostate Cancer Index (PCI) comprised the HRQoL Qx. A 10-item survey designed to measure patient preference of administration was administered after completion of both modalities. Descriptive statistics, Pearson correlation coefficients, and percent agreement were used to assess comparability between these two methods of administration. RESULTS: A convenience sample of 245 subjects volunteered to participate; 209 (85%) completed both paper and online Qx. Subject median age was 63 years-old (range 46-83). The majority of respondents were white (97%), college educated (66%) and had an income of > $75,000/year (46%). With few exceptions, correlation coefficients for the HRQoL multi-level items were high (0.66-0.97) and the percent agreement for yes/no items was also very high (>0.89). Subjects rated both methods of administration favorably, although the Internet was rated as somewhat more convenient and faster to complete. There were no differences between the two versions on respondent ratings for ease of reading, ease of answer completion, confusion or stress. 70% preferred the Internet mode; 21% had no preference and 9% preferred paper. CONCLUSIONS: Administration of the HRQoL Qx, including SF-36 and PCI domains, demonstrated a high correlation between the Internet and the paper-and-pencil methods. The Internet was a well-accepted mode among this select group of older men with prostate cancer.