Heavy menstrual bleeding (HMB) can negatively influence physical activity, work productivity, and sexual life and therefore has a major impact on women's quality of life (QoL). The National Institute for Health and Care Excellence guidelines recommend the levonorgestrel-releasing intrauterine system (LNG-IUS) as the treatment of first choice for HMB. Surgical treatments for treating HMB in women without future pregnancy wish include endometrial ablation (EA) and hysterectomy. Because of potentially biased studies and conflicting results on bleeding scores, satisfaction, and reintervention rate, there is no consensus on the efficacy of LNG-IUS versus EA. This multicenter, randomized controlled, noninferiority trial aimed to compare the effectiveness of the LNG-IUS system with EA in women with HMB. This study was performed between 2012 and 2016 in 26 hospitals in the Netherlands. Women were considered eligible if they had a diagnosed HMB with a Pictorial Blood Loss Assessment Chart (PBAC) score exceeding 150 points, were older than 34 years, had no pregnancy wish, and had no abnormal cervix cytology in the past 5 years. Participants were randomized in a 1:1 ratio to either the LNG-IUS or EA cohort. The LNG-IUS cohort had implantation of the device containing a total of 52 mg of levonorgestrel, releasing 20 μg/d. The EA intervention was performed with a bipolar radiofrequency device either in the office under local anesthetics or in the operating room under general or spinal anesthesia. The primary study outcome was menstrual blood loss at 24 months after randomization in PBAC, measured by participants through standardized questionnaires. Participants completed questionnaires before treatment and at 3, 6, 12, and 24 months after randomization. The primary analysis was an intention-to-treat analysis with a hypothesis that LNG-IUS would be noninferior to EA. Noninferiority of the LNG-IUS protocol would be established if the upper limit of the 95% confidence interval (CI) for the difference in PBAC score did not exceed the predetermined noninferiority margin of 25 points with P < 0.05. A total of 270 participants were randomized to initial treatment with LNG-IUS (n = 132) or treatment with EA (n = 138) between April 2012 and January 2016. A total of 247 participants (91%) reported PBAC scores at 24 months. The mean PBAC score was 64.8 in the LNG-IUS group compared with 14.2 in the EA group (mean difference, 50.5; 95% CI, 4.3-96.7). Noninferiority of LNG-IUS could not be demonstrated (noninferiority, P = 0.87). At 3 months of follow-up, 60% of women in the LNG-IUS group had reached a PBAC score of less than 75 points compared with 83% of women in the EA group (relative risk, 0.72; 95% CI, 0.59-0.87). The LNG-IUS was removed in 49 women (39%), and those in the LNG-IUS cohort were more likely to receive a surgical or drug reintervention within 24 months compared with women in the EA group (35% vs 20%; relative risk, 1.77; 95% CI, 1.17-2.68). There was no statistically significant difference in participant satisfaction and QoL between the cohorts. This study found that both the LNG-IUS and EA protocols for HMB led to a large decrease in menstrual blood loss, with LNG-IUS resulting in an increased risk of needing additional treatment and EA achieving a greater decrease in blood loss, with comparable QoL and satisfaction scores. Noninferiority of LNG-IUS compared with EA could not be demonstrated.