ABSTRACT Background: Endodontic microflora comprises of multispecies, hence no single intracanal medicament can disinfect the root canal completely. Newer herbal medicaments need to be researched which may be more effective. Hence there was a need to evaluate and compare the effect of Septilin and calcium hydroxide intracanal medicaments on interappointment flare up and healing in apical periodontitis. Aim and objective: To evaluate and compare the effect ofcalcium hydroxide and septilin intracanal medicaments in interappointment flare up and periapical healing. Materials and Methods: Thirty patients with periapical lesions in the anterior region of jaw were selected. Intracanal medicaments were inserted as Group I -Calcium hydroxide(n=15) and Group IISeptilinTM (n=15). After 7 days the intracanal medicament was changed and obturation done after 15 days. Patients were evaluated clinically for VRS pain score at 1&2 weeks and 1, 3 and 6 months. Radiographic evaluation using PAI index was done by two trained observers at interval of 1, 3 and 6 months. Results: showed no incidence of flare up. After three months there was significant change in the PAI score. At 6 months, 20% of calcium hydroxide group whereas 13.33% of SeptilinTM group had PAI score of 1. Conclusion: At 3 months the periapical healing in both groups was similar. At 6 months Calcium hydroxide group showed better healing as compared to SeptilinTM group.