Abstract Background In contrast to the increasingly rigorous endpoints of clinical trials of ulcerative colitis (UC), Mayo endoscopic score (MES) ≤ 1 is mostly set as target during clinical follow-up, but long-term outcomes may differ according to different level of healing. Therefore, our study aimed to compare the long-term outcomes of UC patients in clinical remission with different MES and UCEIS scores in real-life condition. Methods UC patients in clinical remission (defined by pMayo<2 with no rectal bleeding) who underwent colonoscopy between 2016-2020 were consecutively enrolled in this multicenter retrospective study. Mayo and UCEIS endoscopic scores were evaluated and clinical and demographic data were collected at baseline. Clinical flare, colectomy, hospitalization and treatment modifications were recorded during at least 3 year of follow-up. Primary outcome was the clinical flare, while secondary outcomes were hospitalization, colectomy, new biological initiation and biological dose escalation during follow-up. Outcomes were compared with Log-rank test and survival characteristics were plotted. Results In total, 156 UC patients were enrolled with a median age of 46.0 (IQR 35.5-58.0), while male/female ratio was 49.4 % (Table 1.). Near to half of the patients (44.9%) had MES>0 endoscopic activity at baseline. Non zero baseline MES (Figure 1.; p = 0.002; MES 0 vs 1 p = 0.004) and UCEIS (p < 0.001; UCEIS 0 vs. 1 p = 0.016) scores were associated with higher rate of clinical flare. Higher baseline MES (p = 0.042) and UCEIS (p = 0.008) scores were coupled with increased risk of hospitalization. Colectomy rates were low. Increased baseline UCEIS (p = 0.003), but not MES score was coupled with new biological treatment initiation, while only UCEIS score was associated with biological treatment intensification (>4; p = 0.008). Conclusion Our study suggests differentiating between complete MH from MES 1 as long-term outcomes were more favorable in case of lower endoscopic scores. Consequently, targeting complete MH should be considered to achieve deep remission and disease clearance.