Background: low –dose ketoconazole (LDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen-independent prostate cancer (AIPC), we hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerabilitiy in the (AIPC). Methods: in a single institution (Tishreen University Hospital, Lattakia), patients with AIPC treated with LDK (at a dose of 200 mg orally 3 times daily ) as secondary hormonal therapy with concomitant steroids were retrospectively identified, After experiencing a rising prostate –specific antigen (PSA) level. Results: 21 of 50 eligible patients)42%) treated with LDK experienced PSA declines ≥ 50% after the start of treatment, while there were 12 patients with low PSA between 25- 50% with a median duration of response (5.4 months) 7 patients less than 25 % decrease, while 10 patients did not never respond. The most common complications is the fatigue and general debility in 18 patients , digestive disorders in 21 patients (Summit, nausea and diarrhea) , muscle disorders in 3 patients, and Metabolic disorders in five patients The incidence of drug toxicity grade 3-4 is very few. There were only three patients not able to continue the treatment due to severe side effects. Conclusion: low dose ketokonazole and Predenisolone is a well – tolerated, relatively inexpensive and clinically active treatment option. PSA response to low – dose ketoconazole historically comparable to that of Abiraterone in patients with AIPC.