OBJECTIVES: The purpose of this study was to validate the health-related quality of life (HRQL) component of a hybrid instrument IMPACT (Impact of Pharmacist Activities and Care on Treatment outcomes) that is being developed to measure patient satisfaction with pharmacist services and HRQL when patients with multiple chronic conditions receive care in a pharmacist-run medication therapy management (MTM) clinic. METHODS: The HRQL component (developed following a systematic literature review and qualitative survey of patient and provider responses) had 24 items in five domains (physical, social, emotional functioning, diet and medication-related issues). The instrument was pretested on second year pharmacy students at our institution to determine its psychometric properties (reliability, construct validity and responsiveness). Student participants received the same baseline scenario (1) of a patient with diabetes, hypertension and dyslipidemia and were randomized to receive one of two endings (2A or 2B). Scenario 2A described patient status where a positive change in health status occurred due to pharmacist intervention and Scenario 2B when there was no change. Participants signed a consent form and completed web-based pre and post HRQL surveys. Reliability was tested using Cronbach's alpha; responsiveness (sensitivity and specificity) using ANCOVA, and construct validity using exploratory factor analysis with varimax rotation. RESULTS: Eighty-five students (2A = 47; 2B = 38) completed the study. Baseline HRQL was not statistically different. The reliability coefficient for the instrument was higher than 80%. ANCOVA showed reasonable responsiveness, i.e., statistically significant differences between Scenario 1-2A and no differences between Scenario 1-2B, as expected. Factor analysis indicated 7 factors; some modification would be needed in two of the items. CONCLUSION: Initial validation of an HRQL instrument for multiple chronic conditions indicated good reliability and responsiveness; however minor modifications would be needed to improve construct validity before the instrument is ready for use in a MTM clinic.