The aim of this study was to evaluate patient-reported outcomes of Collagenase Clostridium Histolyticum (CCHi) for Peyronie's Disease. Patients treated with 2–4 cycles of CCHi between 01/2016 and 08/2018 were asked to fill out the “bother domain” of the Peyronie's Disease Questionnaire (PDQ) at scheduled appointments for injections. CCHi cycles involved two injections (0.58 mg) separated by 48–72 hr. During the study, 34 patients were treated, seven patients were excluded due to incomplete baseline values. Mean (standard deviation) PDQ bother domain baseline score was 11.1 (2.6). ANOVA demonstrated statistically significant effects of injections (p <.001) with a decrease in PDQ bother domain scores 6 weeks after the 1st cycle (9.9 [3.3], p =.013), 6 weeks after the 2nd cycle (8.2 [4.0], p =.009) and 6 weeks after the 3rd cycle (6.5 [3.6], p <.001). After 2–4 cycles of CCHi treatment, patients reported changes in penile curvature as “Worse” (0), “No Change” (2), “Little decrease” (10), Decrease (10) and “Significant decrease” (4). After completion of CCHi treatment, 82% of patients still reported that vaginal intercourse was difficult or impossible. Patients with Peyronie's Disease undergoing CCHi treatment reported statistically significant decreases in PDQ bother domain scores. However, most patients still report difficulty with intercourse after treatment.