To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis UC in real life. Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score PMS. Short-term response/remission was assessed at Weeks 4, 8, and 16. A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio OR = 0.2; 95% confidence interval CI = 0.1-0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 OR = 0.5; 95% CI = 0.3-0.7 and higher PMS at Week 8 OR = 0.2; 95% CI = 0.1-0.5 were associated with lower probability of achieving remission at Week 16. A total of 45 patients 40% discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation hazard ratio = 1.5; 95% CI = 1.3-1.6. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.