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Pakistan is a high tuberculosis (TB) burden country with the incidence of 275/100,000 population. Post-transplant tuberculosis was found to be 15% at our centre before Isoniazid (INH) prophylaxis. A randomized controlled trial of INH prophylaxis at our centre showed a significant reduction of tuberculosis. INH prophylaxis was introduced in all patients post-transplant from April, 2009.The occurrence of TB after INH prophylaxis in a high endemic is a concern. Another concern is INH resistance, a systematic review to assess the effect of INH prophylaxis on the risk of INH resistance did not exclude increase resistance; however there is a paucity of data.To find out the frequency of tuberculosis in renal transplant recipients on INH prophylaxis. To re-assess the efficacy of INH prophylaxis in our patients living in a high TB endemic area. To find out the pattern of clinical presentation and the frequency of INH resistance in patients who develop TB on INH prophylaxis.It is a retrospective observational study. The medical records of all patients transplanted from May 2009 till December 2011 at Sindh Institute of Urology and Transplantation Karachi, Pakistan were reviewed. The files were then reviewed till June 2015 with a minimum follow up of 3.5 maximum of 6 years. The occurrence and characteristics of TB, INH tolerability, and INH resistance were noted.A total of 910 patients transplanted during the study period. Eight twenty six (91%) completed one year of INH prophylaxis successfully. Only 13 (1.42%) developed hepatotoxicity attributed to INH. Forty six out of 910 (5%) developed tuberculosis on INH prophylaxis. More than half of them developed 2 years after tasnplant. Around 38 (84%) patients completed anti TB treatment successfully. Three (6%) died of fulminant TB. Five patients had six (13%) rejection episodes (biopsy proven) during TB treatment. One became dialysis dependent. Thirty seven out of 38 patients (97%) tolerated Rifampicin based regimen very well and completed the treatment. Seven patients developed Hepatotoxicity but only 1 needed modified drugs who was also Hepatitis C positive. Graft functions at the end of the study are comparable among both groups. Out of 14 cultures only one isolate was INH resistant (7%).INH prophylaxis is well tolerated with minimal side effects. The frequency of TB has considerably decreased during the first 2 years post transplant on INH prophylaxis. However late occurrence of tuberculosis, after completion of prophylaxis is noted which may reflect high endemicity of TB in our country. We may consider prolonging the duration of INH prophylaxis.We treat almost all the patients with Rifampicin containing regimes successfully and graft function remains stable in majority of the patients.