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Background Azathioprine (AZA) is most commonly used drug worldwide for maintenance therapy in moderately severe ulcerative colitis (UC) patients even in today’s biologicals era. We aimed to investigate mucosal healing (MH) and deep remission rate in patients with UC on long-term AZA therapy. Methods The study included UC patients presenting to KMC Mangalore, India between May 2016 to Feb 2018, who had received AZA for a minimum period of 6 months without discontinuation. All were subjected to colonoscopy and biopsy at baseline and after at least 6 months of treatment. Patients were excluded in case of any concomitant use of other immunomodulator or biological agent. Clinical remission, MH, histologic healing (HH) were defined by partial Mayo score. Results In the study, 198 patients were screened. Fifty-one [26 male, median age 44 (IQR 53–20) years] patients fulfilled the inclusion criteria. Median disease and AZA therapy duration were 36 (IQR 60–24) and 19 (IQR 36–10) months respectively. At baseline partial Mayo score, UCEIS were 7.3±1.05 and 6.4±0.96 respectively. Twenty-three (45%) patients had extensive colitis (E3), and twenty-eight (55%) had left-sided colitis. Clinical remission was achieved in 68%, MH in 47% and HH in 35% patients. Factors evaluated were demographic features, disease duration, AZA dose and duration, CRP, ESR, albumin, partial Mayo subscores, UCEIS subscores and Geobes score. AZA induced statistically significant (p 2 years (50.9% vs 23%; p-0.07). On follow up partial Mayo score Conclusions Our study showed AZA found to be efficacious in achieving mucosal healing in 47% and deep remission in 35% patients.