OBJECTIVE To examine the role and benefits of transcervical fibroid ablation (TFA) in the treatment of submucous and large uterine fibroids. METHODS A subgroup of patients with submucous or large fibroids were analyzed from two prospective clinical trials (FAST-EU and SONATA) of sonography-guided TFA with the Sonata® system. Key outcomes were changes in menstrual blood loss, symptom severity and health-related quality of life on the Uterine Fibroid Symptom and Quality-of-Life Questionnaire, health-related quality of life on the EQ-5D questionnaire, and surgical reinterventions for heavy menstrual bleeding. RESULTS Among 197 women (534 treated fibroids), 86% of women with only submucous fibroids and 81% of women with large fibroids (>5 cm) experienced bleeding reduction within 3 months post-ablation. Overall symptom severity and health-related quality of life showed sustained, significant improvements over 12 months. Additional fibroid mapping of large fibroids with magnetic resonance imaging in the FAST-EU trial showed an average volume reduction of 68%. Among women with only submucous fibroids, the rate of surgical reintervention through 1 year of follow up was 3.7% in FAST-EU and 0.0% in SONATA. CONCLUSIONS With the Sonata system, TFA is an effective single-stage treatment option for non-pedunculated submucous myomata, and larger or deeper uterine fibroids (including fibroid clusters) for which hysteroscopic treatment is not suitable. ClinicalTrials.gov: FAST-EU, NCT01226290; SONATA, NCT02228174.