Abstract Background Poor self-care behaviour is associated with a higher risk of readmission and mortality in patients with heart failure (HF). The interplay between self-care and patient-reported outcomes such as health-related quality of life (QoL) has not been fully established. Purpose To describe the association between self-care and QoL in real-world cohort of HF patients. Methods We conducted an observational, prospective, cohort study of 1120 consecutive patients with chronic HF. We used the modified European Heart Failure Self-care Behaviour Scale 9-item version (EHFSCBS-9) to measure self-care. Scores were inverted and standardized (higher scores indicate better selfcare). To assess QoL, we used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (higher scores indicate worse QoL). Written informed consent, complete clinical and psychosocial information of patients were obtained at baseline. To determine the impact of global self-care and its dimensions (autonomy-based adherence, consulting behaviour and provider-based adherence), multivariate linear regressions models (backwards stepwise methods) to predict QoL were constructed. The multivariate parametric and non-parametric associations between EHFSCBS-9 scoresand the β estimated risk of impairment of QoL (defined as MLHFQ scores ≥ median values) were explored using General Additive Models (GAM). All models were adjusted by age, sex and prognostic factors such as LVEF, NYHA, NT-proBNP levels and recent hospitalization among other well-known determinants of HF severity. Results A total of 484 patients (43%) were women, mean age was 72±11 years, and mean LVEF was 45±17%. Mean MLHFQ scores were 45±24. Mean EHFSCBS-9 scores were 69±28. There was a significant inverse correlation between EHFScBS-9 and MLHFQ scores (r=−0.158; p-value<0.0001). As shown in Table 1, self-care behaviour and its 3 domains were independent predictors of QoL in 7 out of the 16 associations explored. These models confirmed a weak linear relationship between EHFSCBS-9 scores and MLHFQ scores particularly between global selfcare and consulting behaviour dimension with global, emotional and social dimensions of QoL. Interestingly, when QoL was dichotomized as impaired/preserved QoL, GAM showed a significant non-parametric “U-shape” relationship (p-value<0.05) between EHFScBS-9 scores and the risk of impairment in QoL (Figure 1). Conclusions We have shown that self-care behaviour is an independent predictor of health related QoL in HF regardless the level of disease severity. Global self-care and consulting behaviour were particularly and significantly associated with global QoL and emotional and social dimensions of QoL. Interestingly the relationship between self-care scores and the risk of impaired global QoL was non-linear showing a “U-shape” association pointing out that patients with extreme levels of self-care were more likely to experience impairments in QoL. Funding Acknowledgement Type of funding sources: None.