Endoscopic mucosal resection (EMR) is standard therapy for non-pedunculated colorectal polyps ≥20mm. Recently, it has been suggested that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AE), but evidence from a randomized trial is missing. In this randomized-controlled multicentric trial involving 19 centers, non-pedunculated colorectal polyps ≥20mm were randomly assigned to cold or hot EMR. Primary outcome was major AE (perforation or post-endoscopic bleeding). Among secondary outcomes major AE subcategories, postpolypectomy-syndrome and residual adenoma were most relevant. Between 2021 and 2023, 396 polyps in 363 patients (48.2% female) were enrolled for the intention-to-treat analysis. Major AE occurred in 1.0 % in the cold and in 7.9% in the hot group (p=0.001; Odds ratio [OR] 0.12 [95%-CI: 0.03-0.54]). Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group with 0% vs. 3.9% (p=0.007) and 1.0% vs. 4.4% (p=0.040). Postpolypectomy-syndrome occurred with similar frequency (3.1% vs. 4.4%, p=0.490). After cold resection, residual adenoma was found more frequently, with 23.7% vs. 13.8% (p=0.020; OR 1.94 [95%-CI: 1.12-3.38]). In multivariable analysis, lesion diameter of ≥4cm was an independent predictor both for major AE (OR 3.37) and residual adenoma (OR 2.47), and high-grade dysplasia/cancer for residual adenoma (OR 2.92). Cold resection of large non-pedunculated colorectal polyps appears considerably safer than hot EMR, however at the cost of a higher residual adenoma rate. Further studies have to confirm to which extent polyp size and histology can determine an individualized approach (Trial number: DRKS00025170).