Background: Periampullary tumor involves ampullary, pancreatic, biliary and duodenal mucosa, and pancreaticoduodenectomy considered the curative option. Hence, imaging evaluation to describe the lesion is important. Furthermore, certain specific features could help in pre-operative prediction of resectability for periampullary cancers. The aim of this study is to find out any specific perioperative predictor of resectability on periampullary cancers. Patients and Methods: This is an observational cross-sectional hospital-based study done in tertiary hospital, a total of 79 patients were included in the study. Variables such as age, gender, symptoms (back pain, jaundice, etc.), investigations (bilirubin, alkaline phosphatase, etc.), and imaging (Triphasic computed tomography [CT], magnetic resonance cholangiopancreatography, endoscopic ultrasonography, etc.) were studied and the data collected and analyzed using SPSS 20. Results: Male was slightly predominant and male to female ratio was 1:0.9. The mean age was 50 years (SD ±6.54). Triphasic CT abdomen pancreatic protocol was the most effective modality of investigation. High bilirubin (>10 mg/dl) and back pain were statistically significant among patients with unresectable tumor. Conclusions: Back pain and high bilirubin could be helpful in pre-operative prediction of operability of periampullary cancers.