We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer (mCRPC). In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival (PFS) was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months (0.5-8.6 months) for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen (PSA) declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following: 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and <0.2 ng ml(-1), respectively (hazard rate (HR)=4.767, P<0.001); 3.1 and 1.6 months for a baseline testosterone of ≥ 0.1 and <0.1 ng ml(-1), respectively (HR=2.865, P=0.012); 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and <120 g l(-1), respectively (HR=1.605, P<0.001); and 3.0 and 1.9 months for a PSA doubling time (PSADT) of ≥ 2.0 and <2.0 months, respectively (HR=1.454, P=0.017). A risk model was constructed according to the four factors that divided patients into three subgroups of low risk (0-1 factors), moderate risk (2 factors) and high risk (3-4 factors) with PFS values of 3.6, 3.0 and 1.4 months, respectively (HR=1.619, P<0.001). A nadir PSA of ≥ 0.2 ng ml(-1), a baseline testosterone of <0.1 ng ml(-1), a baseline haemoglobin of <120 g l(-1) and a PSADT of <2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.