ObjectiveThe general aim was to meet the need for empirical comparative studies of health-related quality of life (HRQoL) assessment instruments, by evaluating and comparing the psychometric properties and results of three different, widely used, generic HRQoL instruments in a population sample. The specific aims were to evaluate the subscales of the different instruments that measure the same domain and to assess the association between the HRQoL measures and a single-item self-rated health scale.DesignAn observational cross-sectional study.SettingA population-based sample from Gothenburg, Sweden, was studied in 2008 in the WHO MONItoring of trends and determinants for CArdiovascular disease.ParticipantsA total of 414 subjects were included, 77% women, age range 39–78 years.InterventionsThe Nottingham Health Profile (NHP), the Short Form-36 questionnaire (SF-36), the Psychological General Well-Being Index (PGWB) and a self-rated health scale were used.Outcome measuresScores were analysed for their psychometric properties, internal consistency (Cronbach’s α), construct validity (Spearman’s rank correlations and R2coefficients) and discriminative ability for the presence of self-rated ill-health.ResultsPGWB and SF-36 had higher Cronbach’s α scores than NHP. All correlations calculated between the subscales that were conceptually similar were significant (p<0.01). All subscales could differentiate the presence of self-rated ill-health according to the self-rated health scale (p<0.001). The self-rated health scale correlated strongly with all of the three HRQoL instruments used.ConclusionsThere was a high concordance between the instruments within each domain that was conceptually similar. All three HRQoL instruments (PGWB, SF-36 and NHP) could discriminate the presence of self-rated ill-health. The simple and quick self-rated health scale correlated strongly with the more time-consuming PGWB, SF-36 and NHP. The result supports the existence of a strong association between the self-rated health scale and HRQoL in the general population.