OBJECTIVES: The aim was to study health related quality of life (HRQoL) among users of prescription drugs in a population. METHODS: Cross-sectional survey, 20-84 years, in the County of Uppland, Sweden. Five thousand four hundred four (68%) answered the questionnaire. SF-36 was used to measure HRQoL. Self-report with a recall period of two weeks was used to estimate use of prescription drugs. Linear regression analysis was employed for the multivariate analyses controlling for age, sex and co-medication. Non-users were used as the comparison group. RESULTS: A total of 9.7% of the population used drugs for hypertension, 9.5% analgesics, 6.6% hypnotics and/or anxiolytics, 4.2% drugs for asthma, 3.6% drugs for cardiac problems, 2.4% drugs for diabetes, 2.4% antidepressants, and 2.2% used drugs for angina. As expected, users of different drugs had very different patterns of decreased HRQoL. In the Physical Function (PF) dimension users of drugs for angina had the lowest score (-14.2) followed by users of analgesics (-12.3) and users of drugs for diabetes (-7.2). Users of analgesics (21.6) and users of drugs for angina (-17.8) had the lowest scores on Role Physical (RP). Users of antidepressants (-19.4), and users of hypnotics and/or anxiolytics (-17.6) scored lowest in the Mental Health (MH) dimension. The lowest Role Emotional (RE) scores were found among users of antidepressants (-31.3), users of hypnotics and/or anxiolytics (-15.3) and users of drugs for angina (-9.3). The lowest Social Function (SF) scores were found among users of antidepressants (-16.1), and users of hypnotics and/or anxiolytics (-14.5). CONCLUSION: Users of prescription drugs have a reduced HRQoL, the pattern of decrease as compared to the general population varies by type of disease and drug use.