BACKGROUND AND AIMS: Tofacitinib has been approved for the treatment of patients with moderate-to-severe ulcerative colitis independently of prior therapies. We aimed to assess the efficacy and safety of tofacitinib in biologic-naive patients. METHODS: This was a retrospective analysis of prospectively collected data extracted from the notes of patients with moderate-to-severe ulcerative colitis naive to advanced therapies, who were treated with tofacitinib [10 mg twice daily (b.i.d.) for 8 or 16 weeks followed by a 5 mg b.i.d. maintenance dose] in six Greek Hospitals, who had a follow-up of at least 26 weeks after treatment initiation. RESULTS: Overall, 48 patients were included. Clinical response was seen in 30 (62.5%) and 32 (66.6%) patients at week 8 and 16, respectively. Clinical remission, corticosteroid-free clinical remission, biochemical response, and endoscopic remission at week 26 was observed in 26 (54.2%), 26 (54.2%), 28 (60.8%), and 29 (60.4%) patients, respectively. No major adverse events or infections were recorded. CONCLUSION: In this retrospective ongoing cohort study, tofacitinib demonstrated clinical response at weeks 8 and 16 in more than 60% and steroid-free clinical remission at week 26 in more than 50% of biologic-naive patients with moderate-to-severe ulcerative colitis with a good safety profile, indicating that tofacitinib is an effective first-line treatment for this group of patients.