Background: Post-operative Pancreatic Fistula (POPF) is a potentially life-threatening complication after pancreatoduodenectomy. The aim of present study is to find out the incidence of POPF after pancreaticoduodenectomy, to find out the possible risk factors of POPF. Methods: The present retrospective research was done at “Department of gastroenterology of a tertiary care centre” for a period of six years from January 2018 to December 2023 among 110 patients who had undergone pancreaticduodenctomy. Demographic, pathological & intraoperative data was recorded & results were analyzed using SPSS version 25.0. Results: The average age of patients was 52.7±10.8 years. Out of 110 patients 65.5% were male & 34.5% were females. The mean BMI was 23.5±3.6 kg/m2. Different type of diagnosis found were perampullary carcinoma (46.3%), CA head of pancreas (22.4%), NET (7.6%), distal cholangio carcinoma (8.2%) & others (15.5%). The mean blood loss was 362 ml. The mean value of salivary amylase at day 1 was 296.7 & at day 2 was 91.3. ICU stay was 4.8 days & mean post OP stay was 12.9 days. Mean PD size was 4.58 mm. Co-morbidity was present in 49.5% patients. 60.5% had soft pancreatic texture, SSI was present in 11%, sepsis was found in 19% patients, POPF was present in 35%. A soft pancreatic texture, a main pancreatic duct diameter <4mm, blood loss more than 350 ml, carcinoma head of pancreas & the serum amylase level were independent predictors of POPF (P<0.05). Sensitivity & specificity of serum amylase on POD 1 to predict CR POPF were 82.5%, 42.3% respectively. PPV, NPV, accuracy was 42%, 81.9%, 55.41% respectively. Conclusion: A soft pancreatic texture, a main pancreatic duct diameter <4mm, blood loss more than 350 ml, carcinoma head of pancreas & the serum amylase level were risk factors for pancreatic fistula after pancreaticoduodenectomy.