Objective: Anastomotic leak can adversely affect the outcome of surgery especially if detected late. The present study was carried out to detect the anastomotic leak early in the postoperative period using serial estimation of procalcitonin (PCT) and C-reactive protein (CRP). Material and Methods: A single centre prospective cohort study was done on patients undergoing elective gastrointestinal surgery with anastomosis. Serial estimation of serum procalcitonin and C reactive protein was done on the first five postoperative days. Other parameters such as hemoglobin, total protein, albumin and WBC counts were noted perioperatively. Patients were followed up to 60th postoperative day to assess for anastomotic leak, wound infection and other septic foci. Results: Eighty-four patients were included in the study. Anastomotic leak rate was 26.19% (22/84) and 3/22 patients died in the anastomotic leak group. Wound infection rate was 23.81%. The cut off value of CRP on third postoperative day in detecting anastomotic leak was 44.322 mg/dl with sensitivity of 72.73%, specificity of 66.13% and accuracy of 59.52%. The cut off value for WBC count measured perioperatively in detecting anastomotic leak was 9470 cell/mm3 with sensitivity of 72.73%, specificity of 56.45% and accuracy of 59.74%. Serum procalcitonin, haemoglobin, total protein and albumin measured were not sensitive enough to detect the anastomotic leak early. Conclusion: Measuring CRP on the third postoperative day can predict anastomotic leak with a cut off value of 44.32 mg/dl. Patients with raised CRP need careful evaluation to rule out anastomotic leak before deciding on early discharge.