Objective: Initial orthograde root canal therapy (RCT) is common; an estimated 16 million root canal therapies are performed annually in the U.S. RCT patients frequently experience pain during various stages of their care. The ability of dentists to ameliorate pain-related outcomes makes this an important area for study. We present observational data on pain intensity and pain interference experienced by RCT patients. Method: A total of 62 dentist practitioner-investigators (46 generalists, 16 endodontists), practicing in five geographical areas of The Dental Practice-Based Research Network (DPBRN; www.DentalPBRN.org), enrolled patients requiring RCT. Data collection, via patient self-report, occurred before initiation of treatment, immediately following treatment, and 1 week after treatment to measure pre-operative, intra-operative and post-operative pain. Pain intensity and interference were measured using the Graded Chronic Pain Scale (0-10), while analgesic intake and adequate anesthesia were dichotomous outcomes. Result: 708 patients were enrolled over a 6-month period. Mean (S.D) pain intensity during the week prior to treatment was 3.6/10 (2.9); worst pain was 6.7/10 (3.0) with 50% experiencing severe pain (=7/10). Pre-operatively, 65% of patients reported taking analgesics and the mean (S.D.) number of days with pain was 0.5 (1.2). Intra-operative pain was 1.1/10 (1.9) and adequate local anesthesia was reported by 91%. In the week following treatment, worst pain was 4.3/10 (1.4), and 16% of patients experienced severe pain. Post-operatively, 55% of patients took analgesics and the mean (S.D.) number of days of pain interference was 0.3 (1.0); 6% reported severe pain plus regional swelling. Conclusion: The typical endodontic patient experienced moderate amounts of pain and one-half day of pain interference during the week before treatment. The majority experienced minimal intra-operative pain and adequate anesthesia. Severe pain within the first week post-operatively was reduced, but was still reported by 1 in 6 patients.