Current study was to evaluate the effectiveness of nurse-led program in improving mental health status (MHS) and quality of life (QOL) in chronic heart failure (CHF) patients after an acute exacerbation. CHF patients were enrolled after informed consent was obtained and were assigned into the control and treatment group. Patients in the control group received standard care. In the treatment group, patients received standard care plus telehealth intervention including inquiring patients medical condition, providing feedbacks, counseling patients, and having positive and emotional talk with patients. At the third and sixth month after discharge, participants were called by registered nurses to assess Mental Health Inventory-5 (MHI-5) and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Compared to the treatment group, patients in the control group were less likely to have educational attainment ≥ high school degree and have a married status, but were more likely to have diabetes. No significant differences in MHI-5 (68.5 ± 12.7 vs 66.9 ± 10.4) and KCCQ (70.6 ± 12.2 vs 68.7 ± 10.9) scores at baseline between the control and treatment groups were observed. There were significantly differences in MHI-5 (72.7 ± 15.6 vs 65.2 ± 11.4) and KCCQ score (74.2 ± 14.9 vs 66.4 ± 12.1) at 3 months follow-up between control and treatment groups. Nonetheless, at 6 months follow-up, although MHI-5 and KCCQ scores remained higher in the treatment group, there were no statistically significant differences (MHI-5: 65.4 ± 12.8 vs 61.4 ± 10.0; KCCQ: 65.1 ± 12.3 vs 61.9 ± 10.3). After multivariate regression analysis, not receiving nurse-led program were significantly associated with reduced MHI-5 (odds ratio [OR] 1.25% and 95% confidence interval [CI]: 1.14-1.60) and KCCQ (OR: 1.20% and 95% CI:1.11-1.54) scores. Nurse-led program is helpful to improve MHS and QOL in CHF patients after an acute exacerbation. However, these achievements are attenuated quickly after the nurse-led intervention discontinuation.