Background <p>Comparison of Transanal Endoscopic Microsurgery (TEM) and Endoscopic Submucosal Dissection (ESD) is based only on retrospective studies. With the aim of comparing the effectiveness of TEM and ESD, a single-center randomized clinical trial (RCT) registered at ClinicalTrials.gov NCT03718351 was undertaken.</p> Patients and Methods <p>patients with rectal adenomas ≥ 3&#xa0;cm were randomized (1:1) to TEM or ESD. The primary outcome was R0 resection rate, the secondary end-points were en bloc resection rate, perioperative morbidity and 2-year recurrence rate.</p> Results <p>between 2018 and 2023, 236 patients were included into the ESD or TEM group (<i>n</i> = 118 each). One patient (0.8%) from the ESD group had conversion to the TEM one. The mean size of lesions was 4.2&#xa0;cm in the TEM vs. 4.1&#xa0;cm in the ESD group (<i>p</i> = 0.39). Perioperative complications (&gt; II by Clavien-Dindo) developed in 20/118 (16.9%) patients after TEM vs. 18/118 (15.2%) patients after ESD (<i>p</i> = 0.9). R0 resection and en bloc removal were 79.7% and 97.5% after TEM versus 67.5% and 85.6% after ESD (<i>p</i> = 0.04 and <i>p</i> = 0.002, respectively). Completion surgery performed in 9&#xa0;(7.6%) and 6 (5.1%) cases, respectively. Those patients were excluded from an analysis of long-term results. Thirty-six patients from the TEM and 48 from the ESD group were lost for the follow up. After at least two-year surveillance, the recurrence rate was identical between the groups: 4/73 (5.4%) in TEM vs. 3/63 (4.8%) in ESD (<i>p</i> = 1.0).</p> Conclusion <p>TEM resulted in a higher R0 and en bloc resection rate comparing to ESD; no difference in the recurrence rate was demonstrated.</p>