A systematic literature review was conducted to identify topical management interventions used in ECF/EAF care and to explore the role of these interventions in fistula closure and long-term fistula management. A search of PubMed, the Cumulative Index of Nursing and Allied Health Literature, and Scopus was conducted to identify English-language articles published from January 2004 to January 2019. The keywords enterocutaneous fistula, enteroatmospheric fistula, negative pressure wound therapy, NPWT, vacuum-assisted closure, VAC, pouch or pouching, troughing, bridging, collection device, dressing, and wound care were used to identify all publications pertaining to the topical management of adult and mixed adult/pediatric patients with an ECF or EAF. Single-person case studies, exclusively pediatric studies, surgical treatment-based, and duplicate publications were excluded. Abstracts were screened for relevance to the research questions, and eligible publications were abstracted and categorized using The Oxford Centre for Evidence-Based Medicine Levels of Evidence. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was used to assess each article for risk of bias and methodological quality. Outcomes of interest included patient demographics, closure rates, fistula classification (type of fistula, fistula output, fistula origin), type of topical treatment, adverse events (pain, new fistula formation, fistula recurrence, mortality), follow-up, long-term management, perifistula skin protection, effluent management, dressing change frequency, and quality of life. Descriptive statistics were presented; no statistical analysis was performed. Of the 983 articles identified, 57 underwent critical appraisal using the JBI checklist for case series. Forty-two (42) did not meet the inclusion criteria, leaving 15, level IV, case-based publications (N = 410 patients). No randomized controlled trials were found. All studies included some form of negative pressure wound therapy. JBI results found that each study was at high risk of bias in more than 2 domains. Interventions were categorized as intubation, occlusion, or isolation of the fistula. Of the 559 fistulas treated, spontaneous closure was reported in 164 cases, with rates ranging from 0% to 100%. Adverse events to treatment included pain (n = 33 patients), new fistula formation (n = 12), and fistula recurrence (n = 1). Sepsis was the leading cause of mortality (n = 29), with reported rates ranging from 0% to 44%. Due to the high risk of study bias and low quality of evidence, the exact contribution of any one intervention could not be established. Results also suggest a high risk of publication bias, and patient-centered outcomes were reported in only 1 study. Although topical management might play a role in fistula closure, it is only as part of a comprehensive plan of care. Future research should focus on developing and using standardized reporting tools, classifications, and outcomes and include patient-centered outcomes such as acceptance, tolerability, pain, and quality of life relating to any one intervention. At this time, the evidence base for management recommendations is limited, suggesting that interventions should mainly be based on practical considerations such as resources and clinician skill.