Objectives: Treatment of asymptomatic necrotic teeth is a common type of occurrence in endodontic practice. Root canal treatment of these teeth sometimes results in pain and /or swelling of varying degree. These severe symptoms upset both the patient and dentist. This study was to compare the effect of prophylactic amoxicillin and placebo in endodontic flare-up in asymptomatic necrotic teeth requiring root canal treatment. This was evaluated by using flare-up index. The influence of age, sex, was compared between flare-up and non-flare-up groups. Using a standardized technique and the same materials eliminated the variability of operator. Study Design: Quasi experimental study. Setting: Department of Operative Dentistry, Lahore Medical and Dental College, Lahore. Period: From January 2018 to December 2018. Material & Methods: 102 patients with asymptomatic necrotic teeth with periapical radiolucency were selected from the Operative Dentistry Department of Lahore Medical and Dental College. Patients were divided into two groups experimental and control, by convenient sampling. One half of the patients were given prophylactic amoxicillin and other half was given placebo one hour before treatment. Results: Flare-up occurred in four of the experimental and seven of the control group patients. Statistical analysis revealed no significant differences between flare-up and non- flare- up patients for age and sex. The data outcome was of qualitative in nature i.e. pain and swelling, they were subjected to Chi-Square test of significance with P value of £0.05. The results demonstrated that 10.8% of the 102 patients had a flare-up. No side effects were observed in the patients who were prescribed amoxicillin. Conclusion: The occurrence of flare-up did not significantly influence by Prophylactic amoxicillin (P= .33).