The aim of this study was to evaluate the efficacy of two passive ultrasonic irrigation (PUI) methods and conventional manual irrigation (CMI) in root canal system (RCS) cleaning. Artificial single-rooted teeth were used. Four lateral canals were made 2 and 7 mm short from the apex. Root canals were filled with a contrast solution. The specimens were divided into four groups (n = 8): PUI1—intermittent flushing; PUI2—continuous flushing; CMI1—at 1 mm; and CMI2—at 3 mm. Micro-computed tomographic images were obtained. New images were taken after the irrigation protocols enabling the evaluation of the contrast solution volume (in mm3) within RCS (main and lateral root canals) in comparison to the initial analysis. The comparison among groups was performed using ANOVA and Tukey’s tests with 5 % significance level. There was no difference among PUI1, PUI2, and CMI1 regarding the contrast solution removal from RCS (p > 0.05). These methods demonstrated greater cleaning than CMI2. At the apical third, CMI2 showed lower cleaning capacity when compared to the other methods (p < 0.05). PUI with intermittent or continuous flushing and CMI with the needle placed 1 mm from the working length were efficient in cleaning the main and lateral root canals. Root canal irrigation plays an important role in cleaning and disinfection of the RCS. Effective apical irrigation is an important procedure during root canal treatment. PUI and CMI (at 1 mm short) were effective in cleaning of the main and simulated lateral root canals.