Purpose: The purpose of this study was to compare the effectiveness of lesion sterilization and tissue repair (LSTR) antibiotic paste comprised of chloramphenicol, tetracycline, and zinc oxide and eugenol (CTZ) versus zinc oxide eugenol (ZOE) pulpectomy in the treatment of primary molars with pulp necrosis. Methods: A total of 70 three- to eight-year-old subjects with 88 primary mandibular molars with pulp necrosis were included. The teeth were randomized to the CTZ group or ZOE group. The time taken to perform both techniques was recorded. The parents of the children and the dentist who performed clinical evaluations were blind to the group assignment, although the radiographic evaluator could see the difference in treatments. Clinical and radiographic assessments were performed at three, six, nine, and 12 months. Results: At the 12-month evaluation, the clinical success was 86.4 percent for CTZ and 90.9 percent for ZOE (P=0.50), the radiographic success was 75.0 percent for CTZ and 72.7 percent for ZOE (P=0.81), and the overall success was 70.5 percent for CTZ and 72.7 percent for ZOE (P=0.81). The mean time taken to perform was 61.4 (±20.5 standard deviation) minutes for CTZ and 145.1 (±53.2) minutes for ZOE (P<0.001). Conclusions: At 12 months, both techniques presented no significant difference in success rates for nonvital pulp therapy in primary molars with necrosis. The lesion sterilization and tissue repair procedure time using chloramphenicol, tetracycline, zinc oxide, and eugenol was significantly shorter than for a zinc oxide eugenol pulpectomy.