Introduction: Persons with heart failure (HF) and diabetes mellitus (DM) have great variability in their self-care activities which may conflict or compete. An integrated HF-DM self-care intervention yielded positive effects on HF quality of life (QOL), improved physical activity and improved physical functioning (PF). A greater understanding of the predictors of PF and QOL and relationship to self-care behaviors may improve precision of intervention approaches.Purpose: To identify the demographic, clinical and behavioral factors associated with positive change in PF and QOL in response to the intervention.Methods: Methods: HF-DM participants (n=134), 57.4 ± 11 years, 66% men, 69% African American, were randomized to usual care (UC) or intervention (INT) with assessments at baseline (BL), and 6 months (M). Intervention included education/counseling about HF-DM self-care (diet, medications, self-monitoring, symptoms, and enhanced emphasis on physical activity), home visit after hospital discharge, and monthly phone calls. Demographic (age, gender, race, education) clinical (NYHA class, years with HF and DM, BMI, and Comorbidity index, HF (SCHFI) and DM (SDSCA) self-care behaviors and DM self- efficacy (PDSMS) were examined in relation to PF (6MWT) and QOL (MLHFQ). Sequential linear regression with stepwise variable selection was used to develop parsimonious models with t-tests, ANOVA, Chi square and logistic regression adjusting for BL values.Results: For 6MWT, DM self-care behaviors of exercise and blood glucose monitoring were predictive of improved 6MWT by 45.7 and 35.8 feet respectively (adj R2= .14, p= .001). When considering INT group only, for each 1 day increase in SDSCA foot care, 6MWT distance increased by 47.6 feet (p=.04). For MLHFQ score, SDSCA General Diet lowered MLHFQ by 4.021 points. For each 1 point increase in PDSMS, MLWHF increased by 0.807 points. For every 50 meter improvement on 6MWT, the MLWHF improved by mean 3.263 points (adj R2 = 0.436, p<.001).Conclusions: PF and QOL in HF-DM are associated with DM as well as HF self-care behaviors, and improving DM self-care led to better HF outcomes. Refocusing clinical and research self-care interventions to address comorbid care may lead to improved HF outcomes and QOL.