The purpose of this systematic review was to examine the effectiveness of cognitive behavior therapy (CBT) in minimizing the depressive symptoms and improving quality of life in heart failure (HF) patients with depression. This systematic review was conducted in accordance with the Joanna Briggs Institute methodology for systematic reviews of effectiveness evidence. This review only considered randomized controlled trial, assessing the effectiveness of CBT as a treatment for depression in adults (aged above 18) with HF, compared with usual care, which may include medications. This systematic review includes five RCTs involving 379 HF patients with depression (CBT = 192; Control = 187). Two RCTs compared CBT versus usual care using BDI, and no statistically significant differences were observed in reduction of depression after three months of the intervention (MD ?0.92, 95% CI ?1.89 to ?0.05) (p = 0.06). However, a significant difference of depression level was identified between CBT and control groups in a meta-analysis of two RCTs after 6-months of intervention measured by Hamilton Depression Scale (HAM-D) (MD ?3.34, 95% CI ?5.00 to ?1.68) (p = 0.0001) with moderate heterogeneity (I2 = 43%). Quality of life was assessed at three months between intervening groups undergoing CBT and the control group with usual care in two RCTs. A statistically significant improvement was observed in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) in the CBT group compared with usual care (MD ?9.44, 95% CI ?13.02 to ?5.87) (p < 0.0001). The key finding of this review is that CBT is likely to be helpful in improving the depressive symptoms and quality of life in HF patients with depression. Moreover, long-term continued CBT sessions may help in minimizing the depression level and improving the QoL.