OBJECTIVES: Compliance with drug treatment and health related quality of life (HRQL) are two distinct concepts. However, we might expect a weak positive relationship between the two, i.e. higher compliance is associated with higher HRQL. The purpose of this study was to assess the relationship between compliance and HRQL. METHODS: HRQL was measured using the physical (PCS) and mental (MCS) component summary measures of the MOS Short-Form 12 (SF-12). Compliance was assessed using Morisky’s instrument. Three longitudinal datasets were used to investigate the relationship. One dataset (n=100) included hypertensive patients aged between 34 and 80 years. Another dataset (n=199) covered high risk community-dwelling individuals between 27 and 93 years of age. In this dataset, 43% reported taking medication to control blood pressure. The third dataset (n=365) consisted of elderly patients, of whom 57% reported taking medication for pain relief and 47% to control blood pressure. There are two observations per patient in the first dataset and three per patient in the other two. In all datasets, patients were taking at least one prescribed medication. Correlation coefficients established the relationship between PCS, MCS and compliance. RESULTS: In all datasets, MCS was positively correlated to compliance. PCS was positively correlated to compliance in the hypertensive and the elderly populations and was negatively correlated to compliance in the high risk population. Correlation between compliance and PCS range from 0.00 (p=0.96) to 0.09 (p=0.03). Correlation between compliance and MCS range from 0.01 (p=0.90) to 0.21 (p=0.00). CONCLUSIONS: Correlation between PCS, MCS and compliance was in general positive but typically small or negligible. Further research is needed to establish the relationship between compliance and HRQL.