Background: Health Related Quality of Life (HRQoL) is a relevant variable in the evaluation of health outcomes. Questionnaires based on Classical Test Theory typically require a large number of items to evaluate HRQoL. Computer Adaptive Testing (CAT) can be used to reduce tests length while maintaining and, in some cases, improving accuracy. This study aimed at validating a CAT based on Item Response Theory (IRT) for evaluation of generic HRQoL: the CAT-Health instrument. Methods: Cross-sectional study of subjects aged over 18 attending Primary Care Centres for any reason. CAT-Health was administered along with the SF-12 Health Survey. Age, gender and a checklist of chronic conditions were also collected. CAT-Health was evaluated considering: 1) feasibility: completion time and test length; 2) content range coverage, Item Exposure Rate (IER) and test precision; and 3) construct validity: differences in the CAT-Health scores according to clinical variables and correlations between both questionnaires. Results: 396 subjects answered CAT-Health and SF-12, 67.2% females, mean age (SD) 48.6 (17.7) years. 36.9% did not report any chronic condition. Median completion time for CAT-Health was 81 seconds (IQ range = 59-118) and it increased with age (p < 0.001). The median number of items administered was 8 (IQ range = 6-10). Neither ceiling nor floor effects were found for the score. None of the items in the pool had an IER of 100% and it was over 5% for 27.1% of the items. Test Information Function (TIF) peaked between levels -1 and 0 of HRQoL. Statistically significant differences were observed in the CAT-Health scores according to the number and type of conditions. Conclusions: Although domain-specific CATs exist for various areas of HRQoL, CAT-Health is one of the first IRT-based CATs designed to evaluate generic HRQoL and it has proven feasible, valid and efficient, when administered to a broad sample of individuals attending primary care settings.