Background: Enhancement of the temperature of sodium hypochlorite (NaOCl) solution would increase its cleaning potential and decontamination of the root canal system. Therefore, the aim of the present in vitro investigation was to compare the efficacy of different methods of NaOCl heating by evaluating the temperature profiles developed at different levels of the root canal system. Methods: Five thermocouples were applied at different levels of the root canal system of extracted human premolars. NaOCl solution was heated according to two methods: extraoral heating (50 °C, 60 °C, and 70 °C) using a magnetic hotplate heater and intracanal heating by F-06, XF-30/04, and ML-12 pluggers at 100 °C, 150 °C, and 180 °C. Results: The extraoral heating method was ineffective to produce a significant temperature increase at the root apex. Comparable results were obtained using the intracanal heating method through the ML-12 plugger that showed slightly better results only when set at 180 °C. On the other hand, negligible differences were observed in terms of temperature maintenance at several levels of the root between the F-06 and XF-30/04 pluggers, even though the time intervals were higher in case of XF-30/04. Conclusions: The intracanal heating method provided a better temperature persistence in the middle third of the root canal system. Conversely, extraoral heating was ineffective to produce a significant temperature increase at the apex of the root. Comparable results were obtained even using the ML-12 plugger.