The objective of this study was to assess the efficacy of modern conformal fractionated radiotherapy (RT) in patients with uncured Cushing’s disease (CD) after failed transsphenoidal surgery (TSS). In this retrospective analysis, we reviewed records of patients with CD who received modern conformal fractionated RT between 2001 and 2010. Records were evaluated for frequency and interval of remission post RT. The change in the tumour size, endocrine insufficiencies and complications developing post RT were noted. Remission was defined as 2 mg Low dose dexamethasone suppressed cortisol of <50 nmol/l. During the study period of 10 years, a total of 24 patients (mean age: 27.9, range: 21–48 years) underwent pituitary RT for CD. Out of these, long term follow up was available for 22 patients and 20 patients (15F/5M, 12 microadenomas/8 macroadenomas) were included for final analysis. All the patients received modern conformal fractionated external beam RT (45 Gy in 25 fractions) with the median follow up of 37.5 months (range 12–144). Fifteen patients (10 microadenomas/5 macroadenomas) underwent remission after a median follow up period of 20 months. None of the patients had recurrence. Post RT, new onset endocrine deficiencies were seen in 8 (40 %) patients. Modern conformal fractionated external beam radiotherapy is an effective modality for treatment of adult patients with CD after failed TSS.