This research expands on our prior study, in which we assessed pain reduction after topical doxepin rinse in patients with oral mucositis resulting from cancer and cancer therapy. We continued to enroll patients with painful oral mucositis attributable solely to cancer therapy and performed further analysis on the duration of pain reduction. Fifty-one patients with oral mucositis were enrolled. Mucositis was scored and oral pain was assessed with a visual analog scale before doxepin oral rinse (5 mg/mL) and at regular intervals up to 4 h after rinsing. Of those who reported pain reduction, 95% did so within 15 min of rinsing with doxepin. In the total sample, the average patient reported a 70% maximum decrease in pain (P < 0.0001). Recurrence of pain was slow and at the conclusion of the study 19 patients (37%) still reported a reduction from baseline pain. With this censored data we used Cox-proportional hazards to determine what variables best explained longer duration of pain reduction. Our final model determined that more severe baseline pain, worse mucosal erythema score, or a larger relative maximum reduction in pain were all associated with a slower rate of pain recurrence after oral rinsing (all P < 0.01).