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Purpose: To compare tris-acryl microspheres and polyvinyl alcohol (PVA) microspheres as embolic agents in uterine artery embolization (UAE) for uterine leiomyomas in terms of clinical outcome, inflammatory response, and adverse reactions., Materials and Methods: A double-blinded randomized controlled trial was performed, with 27 patients in the tris-acryl microsphere group and 29 in the PVA microsphere group. The primary endpoint was clinical success, defined as a 2-year freedom from subsequent surgery as a result of persistent or deteriorated symptoms. Secondary endpoints included (i) posttreatment leiomyoma enlargement, (ii) leiomyoma volume reduction at 3 and 9 months, (iii) significant residual intratumoral perfusion, (iv) increase in inflammatory and stress markers, (v) incidence of complications, and (vi) duration of hospital stay., Results: There was no statistically significant difference between the two groups in patient demographics, clinical presentation, initial tumor findings, change in inflammatory and stress markers after treatment, incidence of complications, and duration of hospital stay. Tris-acryl microspheres were associated with a higher rate of clinical success than PVA microspheres (96.3% [26 of 27] vs 69% [20 of 29]; P = .012), a lower incidence of posttreatment leiomyoma enlargement (P = .030), and a lower incidence of significant residual intratumoral perfusion (P = .030)., Conclusions: In the treatment of uterine leiomyomas, UAE with tris-acryl microspheres was associated with a higher clinical success rate, a lower incidence of tumor enlargement, and no significant differences in adverse reactions and inflammatory response compared with the use of PVA microspheres. Tris-acryl microspheres therefore represent the preferred agent for UAE of uterine leiomyomas., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)