BACKGROUND: Tofacitinib is a Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Prospective real-world data are scarce. OBJECTIVES: To collect data on clinical outcomes, including health-related quality of life (HRQoL) and fatigue during treatment with tofacitinib. DESIGN: This is a prospective observational multicentre study in Sweden. In this analysis, outcomes at weeks 2, 8 and 16 are reported. METHODS: Patients with active UC confirmed with endoscopy or faecal calprotectin (FC) were enrolled during 2020-2023 when starting tofacitinib therapy. RESULTS: In total, 103 patients were included. After 2 weeks of treatment, 50% (39/78) had achieved symptomatic response and at week 16, 39% (35/89) had achieved corticosteroid-free clinical remission according to the partial Mayo score. At week 16, a reduction in FC by ⩾50% was seen in 49% (35/71) and 24% (11/46) were in endoscopic remission. The frequency of arthralgia decreased from 29% (30/103) at baseline to 11% (10/89) at week 16. Regarding HRQoL at week 16; each of the four Short Health Scale dimensions (symptoms, social function, disease-related worry and general well-being) had improved by a median of 1 point (p < 0.01) and the European Quality of Life 5 Dimensions 5 Levels index improved from 0.80 to 0.87. Finally, the Inflammatory Bowel Disease Fatigue score measuring occurrence and severity showed an improvement with a decrease from 9 points at baseline to 6 at week 16 (p < 0.05). CONCLUSION: Induction therapy with tofacitinib therapy was associated with improvements in patient-reported outcome measures of symptoms, endoscopic activity, arthralgia, HRQoL and fatigue. These real-world data illustrate that tofacitinib is a fast-acting drug with broad therapeutic effects in UC. CLINICALTRIAL REGISTRATION NUMBER: NCT04338204.