Background Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Methods We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re-treated with AA following prior treatment with AA at the Princess Margaret Cancer Centre. Result All men were heavily pre-treated for mCRPC with a median of four prior lines of therapy, one of which was AA (given either pre- or post-chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of AA due to progression and one stopped for financial reasons. Seven men had a PSA decrease ≥50% following their first AA treatment, of which three (46%) had a PSA decrease ≥50% to AA re-treatment. The responses to AA re-treatment were generally short-lived with a median biochemical progression-free survival of 2.3 months and median treatment duration of 3.2 months. No PSA responses to AA re-treatment were seen in five men who did not have an initial PSA response to AA. Cconclusions Our data suggest that AA re-challenge may have limited benefit in select men with mCRPC, and warrants further formal research. Prostate 74:1462-1464, 2014.