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Mild cognitive impairment (MCI) is prevalent in heart failure, and can contribute to poor self-care and higher hospital readmissions. Strategies to improve self-care in patients with MCI have not been studied. This randomized controlled trial aimed to test the effect of a targeted intervention on self-care, heart failure knowledge, and 30-day readmissions.The study included 125 patients hospitalized for exacerbation of heart failure who screened positive for MCI. The treatment group received a targeted self-care teaching intervention using principles of cognitive training. Self-care, heart failure knowledge, depression, and social support were assessed at baseline and 30 days post-discharge. Mean heart failure knowledge scores improved significantly in the intervention group, but decreased in the control group (P < 0.001). When controlling for other variables, patients in the intervention group showed a greater increase in heart failure knowledge than patients in the control group (P = 0.027). Black race was significantly associated with lower heart failure knowledge scores (P = 0.030). Mean change scores for self-care showed greater improvement in the intervention group when compared with the control group; however, this was not statistically significant. There was no difference in readmission rates between the groups.It is feasible to conduct a randomized controlled trial in patients with MCI. Patients in the treatment group had greater heart failure knowledge at 30 days post-discharge; however, this did not impact readmission rates. Further research is needed to describe how MCI affects self-care and knowledge, and how race and other factors may influence outcomes in this population.