Uterine fibroids are common benign tumors of the uterus. Treatment options include various medical, surgical, and radiological approaches. Magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) is a relatively novel, noninvasive, uterus-sparing technique for treating fibroids. However, not all fibroids can be successfully ablated with MR-HIFU; fibroid perfusion is one of the most important prognostic factors for treatment success. This study investigated the safety and efficacy of MR-HIFU in the treatment of fibroids. The effect of administration of oxytocin on fibroid blood flow was assessed by comparing dynamic contrast enhanced MR images obtained without and with administration of oxytocin to 17 women with uterine fibroids and 11 controls. In addition, the effect of MR-HIFU on ovarian reserve was evaluated by measuring the anti-Müllerian hormone (AMH) levels of 74 women before treatment and three months afterward. The efficacy of MR-HIFU in reducing fibroid-related symptoms and improving the patients’ quality of life (QoL) was assessed using the fibroid-specific Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire up to 12 months post-treatment in 174 women. The effect of the treatment on the two primary fibroid-related symptoms, bleeding and bulk symptoms, was further analyzed in 163 women presenting with an isolated symptom. Major part of these participants overlapped with those included in the earlier study. The findings showed that oxytocin significantly reduced uterine fibroid blood flow, from a median of 39.9 (IQR 21.9–134.5) ml/100 g/min to 3.5 (IQR 2.1–12.1) ml/100 g/min (p < 0.0001, power = 0.87). MR-HIFU did not affect the ovarian reserve significantly: the median AMH was 1.20 (IQR 0.72–2.21) μg/l before treatment and 1.23 (IQR 0.66–2.37) μg/l three months afterward (p = 0.90). MR-HIFU effectively alleviated fibroid-related symptoms, bleeding as well as bulk symptoms. At 12 months, compared with baseline, QoL scores had improved and symptom severity had decreased significantly (p < 0.01). These improvements were observed across all symptomatic patients and in the subgroup with isolated bleeding or bulk symptoms. In conclusion, MR-HIFU was a safe and effective treatment for relieving fibroid symptoms and for improving quality of life over a 12-month follow-up period. Oxytocin reduced fibroid blood flow effectively and may serve as a potential adjunct for enhancing treatment efficacy.