Introduction: Vasculogenic ulcers (Venous, Arterial and/or Mixed) are the most common causes for ulcers in the inferior members, may last from weeks to years.1 Venous leg ulcer (VLU), results from damage to superficial and/or deep vein valves that impairs venous return, compromises the supply of oxygen and tissue growth factors.1 In arterial ulcer, the interruption or decrease of blood flow results in tissue ischemia and cell death1. Combination of chronic venous insufficiency and peripheral arterial occlusive disease characterize mixed leg ulcers.1 Hospitalization is frequent, due VLU complications such edema and infection, in extreme cases the amputation.2 VLU affect patients’ life quality due pain and social distress1. VLU treatment costs are high.2 VLU do not progress in the normal physiological phases of healing, remaining in the inflammatory phase1. Increased levels of metalloproteinases (proteases) in the inflammatory phase destroy proteins essential for extracellular matrix (ECM) formation.3 Without these proteins, angiogenesis does not occur degrading ECM cellular adhesion, delaying healing.3 ECM is the largest component of normal skin, involving cells embedded in a hydrophilic polysaccharide gel3. ECM is composed by proteins (fribonectin, collagen), glycosaminoglycans, proteoglycans and glycoproteins that confer strength, elasticity, hydration and skin resistance.3 Matrix products differ from each other by their source: containing living cells or biologically inert, composed by: biological (animal, human, plant), synthetic and composite materials (biological and synthetic).4 Acellular matrix products are processed to remove cells leaving only the collagen matrix.4 Some products use other ECM proteins (e.g. non-collagen ECM)5. These matrix technologies aim to stimulate or replace the damaged matrix to optimize wound healing.5 Matrixes provide tissue scaffold for cellular base, allowing cellular interaction for migration, proliferation and differentiation, promoting re-epithelialization, revascularization and closure of the VLU.3,5 Therefore, studies demonstrated that ECM products are good option for hard healing vasculogenic ulcers, and, there is scope for further improvement with them. Objective: To synthesize the best evidence on the cost-effectiveness of extracellular matrix products applied as dressings or in topical form in the treatment of venous, arterial and mixed leg ulcers. Method: Systematic Review Protocol, using JBI-SUMARI (software for the systematic literature review - Joanna Briggs Institute). Will be realized searches in databases, thesis registers and clinical trial records to obtain published and unpublished studies. Two independent reviewers will select the studies, applying the following inclusion criteria: participants (adult over 18 years with venous, arterial or mixed leg ulcers in any setting - hospital, clinic, outpatient clinic, long stay institution, home care), intervention (extracellular matrix products applied as dressings or in topical form), comparator (compression therapy alone, any type of dressing, topical agents, standard treatment, and placebos), outcomes (complete healing, time to complete healing of ulcers, adverse events -infection-, reduction of area, pain control, quality of life and costs) and study types (Randomized Controlled Trials, Quasi-Experimental Studies (non-randomized experimental studies), Cohort Studies, Case Control Studies and Case Series, in English, Portuguese or Spanish). After, two independent reviewers will evaluate the methodological quality, extract data, synthesize and evaluate the confidence of the studies (using GRADEPro GDT software).