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Introduction Surfactant-based wound dressings have been utilized in chronic, non-healing wounds and small burn wounds to soften and aid removal of wound debris. In vitro data suggest enhanced healing properties are due to the ability to stabilize and potentially reseal plasma membranes, thereby, retaining cellular integrity and enhance wound healing. Further, surfactant-based wound dressings are non-ionic and may facilitate removal, sensitize, or prevent bacterial biofilms. Biofilms are an evolved, protective mechanism bacteria utilize to reduce antimicrobial efficacy. Removal or penetration of biofilms is essential for bacterial eradication. This case series presents outcomes from use of a water-soluble surfactant dressing (WSD) is used at hospital admission for treating partial thickness (PT) burn wounds. Methods This retrospective, single-center, electronic health record review, included patients, if they were admitted between August 1, 2019 - January 31, 2020, at least 18 years old, and sustained a PT burn wound treated with WSD on admission. Pregnant or incarcerated patients were excluded. The WSD was applied following initial wound debridement, and then twice daily until either discharge or it was deemed burn wound excision would be required. PT tissue salvage was calculated from body mass index (BMI), PT total body surface area (TBSA) burned, and cm2 requiring autografting. SigmaPlot 11.0 was utilized for statistical analysis. Results Thirty-two patients were included. All but one patient had a TBSA burned less than 20% with median (IQR) of 6% (3.5,9). Fifteen also had some full thickness injuries. Seventy-eight percent had flame injuries; 19% contact. Two had inhalation injuries. All but four had a significant past medical and/or social history. Fifty-nine percent had a history of substance abuse and 22% had diabetes. Nine patients had a delayed admission. The median BMI was 26 (24.3,34.2). There were no deaths. Seven patients were discharged within 48 hours to complete outpatient treatment. Median length of stay was 7 days (4.8,12.8). There was lack of any full thickness conversion to the applied areas in 69% of patients; 91% demonstrated either complete or some tissue salvage. Median % PT tissue salvage was 100 (75.3,100). The WSD was well tolerated and no patients developed a wound infection to the applied area. Conclusions Understanding inherent design limitations, this case series demonstrates feasibility of early application, and potential efficacy preventing wound conversion in a complex population with comorbidities and polysubstance abuse.