Abstract Background Crohn's disease (CD) presents heterogeneity in clinical phenotypes. Progression of disease and response to therapy have been associated, among other factors, with the extent and behavior of the disease. Real-world data on long term effectiveness of ustekinumab (UST) in CD based on disease characteristics are limited and conflicting1,2. The aim of this study is to describe real-world UST persistence according to disease distribution and perianal involvement in patients with CD. Methods This was a retrospective multicenter study involving adult patients with CD who received, at least, one dose of UST until August 2023, at 5 major hospitals in Athens, Greece. UST effectiveness based on treatment persistence was evaluated using Kaplan Meier curves for survival free of treatment discontinuation among patients with different disease extent and behavior. Log-rank test was used for statistical significance. Results A total of 147 adult CD patients who received biological treatment with UST for a median of 34 months (IQR 17-48) were included in the study. Patient baseline characteristics are shown in Table 1. UST treatment persistence rates were 93% (95% CI: 89-98) at 12 months and 87% (95% CI: 81-94) at 36 months. The persistence rate of UST differed significantly between patients with or without perianal disease (p=0.036) (Figure 1), while there was no significant difference based on disease extent (p=0.59) or behavior (p=0.31). Conclusion Our study showed that UST treatment persistence is similar in adult patients with CD, regardless of disease localization or behavior. Nonetheless, perianal disease involvement is associated with reduced treatment persistence.