Objective: This abstract reports on the feasibility of conducting a large-scale endodontic prospective cohort study within The Dental Practice-Based Research Network (DPBRN; www.DentalPBRN.org). This study was designed to measure pain occurrence (prevalence, recovery, and incidence) and explore risk factors associated with initial orthograde root canal therapy (RCT). Method: A total of 62 dentist practitioner-investigators (46 generalists, 16 endodontists), practicing in five geographical regions, were DPBRN-certified and trained on a standardized study protocol about RCT. Enrollment and baseline data collection occurred over six months and post-obturation follow-up occurred for another six months. Patients and dentists completed questionnaires before and immediately after treatment visits. Patients also completed questionnaires at 1 week, 3 months and 6 months after obturation. Result: Enrollment exceeded target expectations, with eligible patient-participants totaling 708. Questionnaire return rates by patient and dentist ranged from 90% to 100%. Patient demographics were typical of persons who receive RCT in the U.S.: mean age of 48 years (SD 13 years), with the majority being female (59%), college-educated (81%), White non-Hispanic (86%), and with dental insurance (81%). The tooth types being treated were also typical: 61% molars, 28% premolars, and 11% anteriors, with maxillary teeth (59%) being predominant. Conclusion: This study demonstrates the feasibility of conducting large-scale endodontic prospective cohort studies within DPBRN. Patients were rapidly recruited with high levels of compliance in data collection.