Introduction: The the of this study was to investigate the effect of the orientation of a side-vented needle on the irrigant flow pattern in a C-shaped root canal system using computational fluid dynamics and to evaluate the real-time replacement of irrigant in the lateral canal (LC). Methods: A mandibular second molar with a complete C-shaped canal system was chosen for this study. The root canals were prepared and scanned, and then the images were exported to design software. A 30-G, side-vented irrigation needle was positioned with the open notch facing the lateral canal (case A) and rotated 900, 180, and 270 clockwise (cases B, C, and D, respectively). The flow pattern, irrigant replacement, velocity distribution, wall stress distribution, and apical pressure in the canal were analyzed. Results: Most of the irrigant flowed to the canal outlet from the adjacent instrumented canal space with different trajectories in the 4 cases. The concentration of scalar immediately below the tip of the needle was exchanged quickly; the length of the cleared zone extended 3 mm beyond the tip of the needles. The depth of circulation in the LC in all cases increased during the first 0.2 seconds. After that, the exchange of irrigant reached a stable phase. Irrigant penetration in the LC was greatest in cases A and B (<1.1 mm). Apical pressure in case B was significantly lower than in other groups. Conclusions: The scalar concentration can be used to evaluate the replacement of irrigant in the root canal over time. Orientation of the opening of the side-vented needle influences the flow pattern, velocity, apical wall pressure, and penetration into the LC.