Background: The Laboratory Risk Indicator for Necrotizing Fasciitis score (LRINEC) is a simple tool used to support early diagnosis of Necrotizing Fasciitis (NF). The aim of this study was to investigate whether the LRINEC is suitable as a progression and prognosis parameter in patients with NF. Methods: In this retrospective study, laboratory data of 70 patients with NF were analyzed. The LRINEC was calculated for every patient at the time of hospital admission and postoperatively after surgical interventions. Furthermore, the LRINEC was examined as a prognostic factor for survival. Results: The overall lethality of our series was 20 out of 70 (28.6%). A highly significant LRINEC decrease was found for serial debridements. The largest decrease was observed after the first debridement. There was a significant difference between the initial LRINEC of deceased and surviving patients. A cut off value of >6.5 (7 LRINEC points) resulted in an optimal constellation of sensitivity (70%) and specificity (60%) to predict lethality in patients with NF. Conclusions: The LRINEC significantly decreases after surgical debridement. An initial LRINEC equal or greater than seven is an independent prognostic marker for lethality and can help to identify high-risk patients.