Although motivational interviewing (MI) seems to be promising for enhancing self-care behaviors (i.e., daily disease management and responses to symptoms) in patients with heart failure (HF), no quantitative pooling of effect sizes has been described to summarize and test its efficacy on self-care. Given that self-care behaviors of patients with HF are essential to enhance pharmacological adherence and disease management and optimize clinical outcomes, we sought to perform a systematic review of randomized control trials (RCTs) regarding MI's efficacy on enhancing self-care behaviors among patients with HF, synthesizing MI effects on self-care through meta-analyses. Nine randomized controlled trials were included. MI showed moderate effects on enhancing self-care confidence (Hedge's g = 0.768; 95%CI = 0.326-1.210; P = 0.001) and self-care management (i.e., responses to symptoms) (Hedge's g = 0.744; 95%CI = 0.256-1.232; P = 0.003) and large effects on improving self-care maintenance (i.e., adherence to treatment and symptom monitoring) (Hedge's g = 0.873; 95%CI  = 0.430-1.317; P < 0.001). No significant effects were found for enhancing the self-reported physical functioning (Hedge's g = -0.385; 95%CI = -1.063-0.294; P = 0.267) or the directly assessed physical functioning using the 6-min walking test (Hedge's g = -0.131; 95%CI = -0.981-0.720; P = 0.072). Although future research is still required to identify situation-specific indications regarding how MI should be implemented in relation to specific clinical conditions, this study showed that MI is an effective strategy to improve self-care in patients with HF.