OBJECTIVES: Patients with Heart Failure (HF) are known to be noncompliant and can also suffer from poor HRQoL. We wanted to determine whether compliance influenced HRQoL scores. We used the SF-36 and compliance scores of patients with HF to examine this question. METHODS: These data are from a RCT of patients with HF (n=134) who were assigned to a usual care arm (U) or an enhanced intervention arm (I) and followed for one year. Improvement in HRQoL was considered as an increase in 10 points in the PCS or MCS summary scales of the SF-36 which we considered to be reflective of a minimal clinically important difference (MCID) for patients. Patients who had an overall compliance score between 0.8 and 1.2 were considered compliant. Patients who had an overall compliance <0.8 or >1.2 were deemed non-compliant. Using a logistic regression model with compliance as the dependent variable we entered HRQoL data and ARM allocation. RESULTS: The odds ratio of associated with a 10-point increase in PCS was 1.63 for compliance relative to non-compliance (CI 1.06 - 2.51) p=0.026. The odds ratio associated with a 10-point increase in MCS was 1.26 (CI 0.868 - 1.83) p (ns). When we include the ARM in the model the odds ratio is 1.58 (CI>1.02 - 2.45), p=0.040. CONCLUSIONS: There is a statistically significant relationship (p<0.05) between HRQoL and compliance, where 1.63 can be interpreted as the change in odds of compliance relative to non-compliance that is associated with a 10-point change in the PCS score of the SF-36. These findings help us interpret HRQoL data by including HRQoL as a mediating variable that affects outcomes such as compliance that are known to have a significant impact on patients with HF.