AbstractPhoton-initiated photoacoustic streaming (PIPS) with an Er: YAG laser has been introduced in root canal treatment to improve irrigation and facilitate the removal of bacteria in the root canal system. This study aimed to compare the antibacterial effectiveness of two different root canal irrigation techniques, conventional needle irrigation (CNI) and PIPS, using 1% sodium hypochlorite (NaOCl), in the treatment of teeth with apical periodontitis. Sixty patients with a total of sixty teeth affected by apical periodontitis were included in this study. The teeth underwent root canal therapy, and after mechanical instrumentation, they were randomly assigned to two groups (n = 30) based on the final irrigation protocol: CNI or PIPS with 1% NaOCl. Bacterial suspensions in the root canals were evaluated using Adenosine 5’-triphosphate (ATP) assay kit after mechanical instrumentation and after final irrigation. Then, a follow-up was conducted after 7 days. The results revealed that final irrigation significantly reduced ATP values in both the CNI and PIPS groups (P < 0.001). The ATP values after final irrigation was greater in the CNI group compared to the PIPS group (P < 0.001). After a 7-day follow-up, percussion tenderness and fistula were significantly resolved in both groups (P < 0.05). A multivariate linear regression model was used to identify the factors that influence post irrigation ATP values. The analysis demonstrated that pre-operative percussion tenderness (P = 0.006), the presence of a fistula (P < 0.001) and the method used in the final irrigation (P < 0.001) had a significant impact on the ATP value after final irrigation. These results indicate that employing PIPS with 1% NaOCl as the final irrigation protocol exhibited superior antibacterial effectiveness and has the potential to enhance clinical outcomes in the treatment of teeth afflicted with apical periodontitis.