Introduction: Although often used to effectively treat dentoalveolar pathosis, there is insufficient information about whether initial orthograde root canal therapy (RCT) adequately reduces multiple dimensions of pain. A prospective observational study assessing pain intensity, duration, and its interference with activities among RCT patients was conducted. Method: Sixty-two practitioners (46 general dentists, 16 endodontists) in the National Dental Practice-Based Research Network enrolled patients requiring RCT. Patient reported data were collected before, immediately following, and one week after treatment. Pain intensity and related interference were measured using the Graded Chronic Pain Scale. Results: Over a 6-month period 708 patients were enrolled. Prior to treatment patients reported a mean (±standard deviation) worst pain intensity of 5.3±3.8 (0-10 scale), 50% had “severe” pain (=7), and mean days in pain and days pain interfered with activities were 3.6±2.7 and 0.5±1.2, respectively. Following treatment, patients reported a mean worst pain intensity of 3.0±3.2, 19% had “severe” pain, and mean days in pain and days with pain interference were 2.1±2.4 and 0.4±1.1, respectively.All changes were statistically significant (p<0.0001). Conclusions: There was a significant reduction in pain intensity, duration, and pain-related interference following treatment, but 19% of patients still reported “severe” pain during the post-operative week.