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Background: Physiotherapy can include both device-guided slow breathing (DGSB) and nondevice-guided slow breathing (NDGSB) in the treatment of systemic arterial hypertension., Objective: The aim of this study is to summarize the effects of DGSB on blood pressure levels of patients with hypertension based on the published literature to date., Methods: A systematic search of all published randomized controlled trials (RCTs) on the effects of device-guided and nondevice-guided slow breathing in patients with hypertension, without language restriction, was carried out up to a publication date of January 2020 in nine databases: PubMed/MEDLINE, Latin American and Caribbean Health Sciences Literature (LILACS), EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Physiotherapy Evidence Database (PEDro), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, Web of Science, and Livivo. Clinical trial records databases (ClinicalTrials.gov), and bases for the open gray literature, including Gray Literature Report and ProQuest Central (Citation, Abstract or Indexing, and Dissertations and Theses), were also searched for potentially eligible RCTs. The quality assessment of the included studies will be performed using the Cochrane Risk of Bias Tool for Randomized Trials. The overall quality of the evidence for each outcome will be assessed using the GRADE (Grading of Recommendations, Development and Evaluation) system., Results: As of December 2021, the review was completed and all data from continuous variables referring to blood pressure values (mmHg) were synthesized., Conclusions: This systematic review will provide a summary of the current evidence on the effects of both DGSB and NDGSB on blood pressure levels. This information can contribute to decision-making by health professionals related to the use of these interventions in patients with hypertension., Trial Registration: PROSPERO (Prospective International Register of Systematic Reviews) CRD42020147554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=147554., International Registered Report Identifier (irrid): RR1-10.2196/33579., (©Kamila Shelry de Freitas Gonçalves, Ana Carolina Queiroz Godoy Daniel, José Luiz Tatagiba Lamas, Henrique Ceretta Oliveira, Renata C C P Silveira, Lyne Cloutier, Eugenia Velludo Veiga. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.03.2022.)