Introduction: This study compared the effect of conventional needle irrigation (positive pressure) and the EndoVac system (Discus Dental, Culver City, CA) (negative pressure) on postoperative pain in mandibular molar teeth with symptomatic irreversible pulpitis. Methods: One hundred sixteen patients with symptomatic irreversible pulpitis were selected. Teeth were randomly assigned to 2 groups according to the irrigation methods performed during root canal preparation. In group 1, root canal irrigation was performed using a syringe and a 31-G side-port needle (NaviTip; Ultra dent, South Jordan, UT). In group 2, the EndoVac system was used for irrigation. Teeth were then obturated with gutta-percha and a resin-based sealer using the cold lateral compaction technique. The presence of postoperative pain was assessed after 6, 24, 48, and 72 hours and 1 week. Results: At 6-, 24-, and 48-hour time intervals, group 1 patients reported more intense postoperative pain than patients in group 2 (P < .05). There was no significant difference between the 2 groups at the other time intervals (P > .05), and in both groups the intensity of postoperative pain decreased over time. Conclusions: Apical positive pressure irrigation caused greater postoperative pain after endodontic therapy of mandibular molar teeth with symptomatic irreversible pulpitis compared with the apical negative pressure irrigation system.