Background: Treatment of patients with a significant percentage of total body surface area of deep burns requires intensive care, including conservative therapy and debridement and split-thickness skin grafting surgery. Skin graft failure (SGF) is an absolute indication for regrafting and thus, it increases the number of reconstructive surgeries, prolongs the duration of hospital stay, and increases the risk of hospital-acquired infections. This study aims to identify factors associated with SGF, which can help quantify the risk of skin graft failure and eventually modify the disease course by pharmacological interventions. Methods: A retrospective single centric longitudinal observational study of a cohort of adult burn patients admitted immediately after the injury to the Burn Intensive Care Unit was performed. Results: Sixty-nine burn patients were included. Thirty-three patients (47.8%) underwent at least one regrafting due to skin graft failure. In simple regression analyses, we identified several baseline factors associated with skin graft failure. In multiple regression analyses, after controlling for confounding of percentage of total body surface area of deep burns, white blood cell count remained associated with skin graft failure. Conclusions: Patients with higher baseline white blood cell count have higher risk of skin graft failure compared to those with the same percentage of total body surface area of deep burns but lower baseline white blood cell count. Level of evidence: Level V, risk/prognostic [ABSTRACT FROM AUTHOR]