Introduction Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps < 10 mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift™ (GI Supply, Pennsylvania) in CSP. Methods The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4–9 mm polyps, with or without submucosal injection of EverLift™. Patients 18–80 years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift™. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin −10%). Results A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift™. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI: −2.66 to 5.42%), demonstrating non-inferiority of EverLift™ injection. Use of EverLift™ significantly increased CSP time (109.8 vs 38.8 s, p  < 0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p  = 0.002). Conclusion Submucosal injection of EverLift™ was non-inferior to CSP of 4–9 mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4–9 mm polyps can be safely performed without submucosal injection of EverLift™.