Fistula formation in head and neck wounds is considered one of the most challenging complications that a head and neck reconstructive surgeon may encounter. The current mainstay of treatment is aggressive surgical debridement followed by vascularised soft tissue coverage. Negative pressure wound therapy (NPWT) has been successfully used for the closure of complicated wounds for decades. This study analysed the outcomes and complications of NPWT in the management of head and neck wounds with fistulas. A systematic search of studies published between January 1966 and September 2019 was conducted using the PubMed, MEDLINE, EMBASE, and SCOPUS databases and using the following key words: “negative pressure wound therapy,” “head and neck,” and “fistula.” We included human studies with abstract and full text available. Analysed endpoints were rate of fistula closure, follow‐up duration, and complications if present. Nine retrospective case series (Level IV evidence) that collectively included 122 head and neck wounds with orocutaneous fistulas, pharyngocutaneous fistulas, and salivary contamination were examined. The number of patients included in each study ranged from 5 to 64. The mode of NPWT varied among the included studies, with most adopting a continuous pressure of −125 mm Hg. Mean durations of NPWT ranged from 3.7 to 23 days, and the reported fistula closure rate ranged from 78% to 100%. To achieve complete wound healing, six studies used additional procedures after stopping NPWT, including conventional wound dressings and vascularised tissue transfer. Information regarding follow up was provided in only three of the nine studies, where patients were followed for 5, 10, and 18 months. No serious adverse events were reported. NPWT for head and neck wounds with fistulas may be considered a safe treatment method that yields beneficial outcomes with a low risk of complications. The current data originated mainly from studies with low levels of evidence characterised by heterogeneity. Therefore, definitive recommendations based on these data cannot be offered. Additional high‐quality trials are warranted to corroborate the findings of this systematic review.