Ultrasonic irrigation and syringe irrigation were compared for their efficacy at cleaning root canal in vivo and in vitro. The in vivo study used 60 anterior teeth or premolars from 60 patients with periapical periodontitis who were randomly assigned to a syringe irrigation group (group S) or an ultrasonic irrigation group (group U). After instrumentation with a K-file using the step-back technique, the two groups received ultrasonic or syringe irrigation using 40 mL of 2.5% NaOCl respectively, followed by conventional lateral compaction. The in vitro study used 60 extracted single-canal premolars, which were also divided into U and S groups, and underwent the same irrigation and compaction. Forty of them were evaluated histologically by light microscopy, and the remaining 20 by scanning electron microscopy. No difference in main root canal filling was observed between the U and S groups. Notably, group U had a larger number of obturated lateral canals than group S. Moreover, a smaller amount of organic debris and more open dentinal tubules were observed in the root canal in group U than in group S. Our findings suggest that ultrasonic irrigation has a greater capacity to clean instrumented root canals than syringe irrigation. (J Oral Sci 58, 373-378, 2016).