Background Necrotizing fasciitis (NF) is a serious infection of the skin and soft tissues including subcutaneous tissue and fascia, which rapidly progresses along the deep fascia and becomes a medical and surgical urgency. Delayed treatment is associated with loss of limb and infection and is the most common cause of mortality. The purpose of our study is to identify the risk factors which may be used to predict amputation and mortality in patients with NF. Materials and methods All adult patients presented in General Surgery OPD/emergency and plastic surgery OPD of MGUMST with NF were assessed, admitted, and treated with broad-spectrum antibiotics from January 2019 to June 2020. All routine blood parameters were evaluated and were provided proper emergency surgical treatment. The surgical interventions included incision and drainage, debridement, fasciotomy, and amputation. The clinical data and demographic characteristics within the first day of admission and after 48–72 hours were documented. Important data associated with the investigations and treatment of NF, i.e., wound appearance, site of infection, organisms involved, and laboratory data within the first day of admission and after 48–72 hours, surgical intervention and outcome, were documented. Patients were divided into two groups: survival and mortality which were further grouped into two groups: those with amputation and without amputation. Results Among 100 patients with diagnosis of NF, 20% died and 10% underwent amputation. From multivariable analysis, the predictors of mortality among patients of NF were patients of age >60 years [risk ratio (RR) = 58.57, 95% CI = 3.64–941.85, p = 0.004], having diabetes mellitus (DM) (RR = 28.70, 95% CI = 1.78–461.51, p = 0.017), gangrene (RR = 3.86, 95% CI = 1.91–7.75, p = 0.0002), severe sepsis (RR = 158.14, 95% CI = 9.96–2508.89, p = 0.0003), involvement of multiple sites (RR = 9.06, 95% CI = 4.25–19.31, p = 0.0001), total leukocyte count (RR = 158.14, 95% CI = 9.96–2508.89, p = 0.0003), and serum creatinine (RR = 126.28, 95% CI = 7.92–2013.12, p = 0.0006) on admission and within 48–72 hours of admission and the independent predictors of amputation among patients of NF included having gangrene (RR = 173.73, 95% CI = 10.91–2764.80, p = 0.0003), severe sepsis (RR = 6.00, 95% CI = 1.86–19.26, p = 0.002), total leukocyte count (RR = 6.00, 95% CI = 1.86–19.26, p = 0.002), and serum creatinine (RR = 64.68, 95% CI = 3.92–1064.68, p = 0.003) on admission and within 48–72 hours of admission. Conclusion In our study, we concluded that gangrene, severe sepsis, total leukocyte count >25,000, and serum creatinine values >1.6 mg/dL on admission as well as within 48–72 hours, as independent predictors for both amputation and mortality and some other factors like age >60 years, the involvement of multiple sites, DM mainly predicting the mortality rate independently. How to cite this article Sharma M, Kanojiya R, Goyal S. Evaluation of Risk Factors for Amputation and Mortality in Patients of Necrotizing Fasciitis. J Mahatma Gandhi Univ Med Sci Tech 2020;5(2):38–46.