Abstract Rationale and Aim Advanced Practice Nurse (APN) is a specialist who has acquired clinical skills to make complex decisions for a better professional practice. In the United States, this figure has been developed in different ways, but in some European countries, it is not yet fully developed, although it may imply a significant advance in terms of continuity and quality of care in patients with chronic or multiple pathologies, including cardiac ones and, more specifically, heart failure (HF). The follow‐up of HF patients in many countries has focused on the medical management of the process, neglecting all the other comprehensive health aspects that contribute to decompensation of HF, worsening quality indicators or patient satisfaction, and there are not updated reviews to clarify the relevance of APN in HF, comparing the results of APN interventions with doctors clinical practice, since the complexity of care that HF patients need makes it difficult to control the disease through regular treatment. For this reason, this systematic review was proposed in order to update the available knowledge on the effectiveness of APN interventions in HF patients, analysing four PICO questions (Patients, Interventions, Comparison and Outcomes): whether APN implies a reduction in the number of hospital readmissions, if it reduces mortality, if it has a positive cost‐benefit relationship and if it implies any improvement in the quality of life of HF patients. Design and Methods A systematic review was performed based on the PRISMA statement, searching at four databases: PubMed, CINAHL, Scopus and Cuiden. Articles were selected based on the following criteria: English/Spanish language, up to 6 years since publication, and original quantitative studies of experimental, quasi‐experimental or observational character. Papers were excluded if they do not comply with CONSORT or STROBE checklists, and if they had not been published in journals indexed in JCR and/or SJR. For the analysis, two separate researchers used the Cochrane Handbook form for systematic reviews of intervention, collecting authorship variables, study methods, risks of bias, intervention and comparison groups, results obtained, PICO question or questions answered, and the main conclusions. Results A total of 43,754 patients participated in the 11 included studies for the development of this review, mostly from United States and non‐European countries, with a clearly visible lack of European publications. Regarding the results related to first PICO question, researches reviewed proved that APN implied a reduction in the number of hospital readmissions in patients with heart failure (up to 33%). Regarding the second question, mortality was always lower in groups assisted by APN versus in control groups (up to 7.8% vs. 17.7%). Regarding the third question, APN was cost‐effective in this type of patient as the cost reduction was eventually calculated in 1.9 million euros. Regarding the last question, quality of life of patients who have been cared for by an APN had notoriously improved, although one of the papers concluded that no significant differences were found. All the questions addressed obtained a positive answer; therefore, APN is a practice that reduced hospital readmissions and mortality in HF patients. The cost‐effectiveness is much better with APN than with usual care, and although the quality of life of HF patients seems to improve with APN, more studies are needed to support this focused on this.