Introduction A triple antibiotic mixture of ciprofloxacin, metronidazole, and minocycline was used as an intracanal medicament in an attempt to disinfect the root canal system for revascularization of a tooth with a necrotic pulp. However, discoloration developed after applying the triple antibiotic mixture. Methods Six weeks after a triple antibiotic paste had been applied to the root canal of tooth #8 of a 7-year-old girl, the tooth showed a dark discoloration. An in vitro experiment with human extracted teeth was performed to determine which of the 3 antibiotics caused the tooth discoloration. Another experiment was then carried out to examine whether a currently used dentin bonding agent would prevent or reduce such discoloration. The degree of discoloration was assessed by using a colorimeter. Results Among the components of the triple antibiotic paste, only minocycline caused the tooth discoloration. Moreover, the dentin bonding agent reduced the intensity of the discoloration but did not prevent it. Conclusions The possible esthetic problems with the tooth color should be considered when using minocycline as a canal medication.