Background Data are limited regarding comparison between nonspherical polyvinyl alcohol (PVA) particles and tris-acryl gelatin microspheres (TAGM) in uterine artery embolization (UAE). Purpose To compare pain after UAE with PVA versus TAGM for treatment of symptomatic fibroids. Materials and Methods In this randomized clinical trial, participants were assigned to be administered nonspherical PVA (355-550 μm) or TAGM (500-700 μm). Both groups were administered fentanyl-based intravenous patient-controlled analgesia during the first 24 hours after UAE and rescue analgesics. Neutrophil-to-lymphocyte ratio was measured to assess inflammatory response. Contrast-enhanced MRI 1 day after UAE was used to evaluate dominant fibroid necrosis and ischemia of normal myometrium. Symptom severity score and health-related quality-of-life score were assessed before and 3 months after UAE. Variables measured over time were analyzed by using the generalized estimating equation method. Results A total of 54 participants (mean age, 44 years ± 4 [standard deviation]) were evaluated (27 participants in each group). Although pain scores and fentanyl dose were not different during the first 24 hours, use of rescue analgesics was higher in the PVA group (33% vs 11%; P = .049). After embolization, symptom severity score and health-related quality-of-life score were not different between groups (symptom severity score: 16 [interquartile range, 6-22] for PVA vs 19 [interquartile range, 9-34] for TAGM, P = .45; health-related quality-of-life score: 93 [interquartile range, 80-97] for PVA vs 89 [interquartile range, 84-96] for TAGM, P = .41). Changes in neutrophil-to-lymphocyte ratio from before to 24 hours after UAE were greater in the PVA group (3.9 [interquartile range, 2.7-6.8] for PVA and 2.5 [interquartile range, 1.5-4.6] for TAGM; P = .02). Rates of complete dominant fibroid necrosis were not different between groups, but transient global uterine ischemia of normal myometrium was more frequent in the PVA group (44% vs 15%; P = .04). Conclusion When used in uterine artery embolization, polyvinyl alcohol particles and tris-acryl gelatin microspheres resulted in similar pain scores and fentanyl dose. Polyvinyl alcohol resulted in a greater inflammatory response, higher rates of rescue analgesic use, and more frequent transient global uterine ischemia. © RSNA, 2020 See also the editorial by Spies and Frenk in this issue.