OBJECTIVES To compare indirect utilities for prostate cancer patients obtained with a generic (SF-6D) and a disease-specific instrument (Patient Oriented Prostate Utility Scale, PORPUS-U). METHODS This was a cross-sectional study of 480 prostate cancer patients enrolled in two similar prospective cohorts. The first one included men diagnosed in 2003-2005 with localized prostate cancer (stage T1 or T2) treated with radical prostatectomy, external radiotherapy, or interstitial radiotherapy at 10 hospitals. The second cohort included patients with stage T2 or T3, treated with external radiotherapy alone or combined with brachytherapy, recruited in 2003–2006 at 6 hospitals. Annual computer-assisted telephone interviews carried out in both cohorts included several questionnaires: the SF-36v2 (from which is derived the SF-6D), the PORPUS-U, and the Expanded Prostate Cancer Index Composite (EPIC), measuring urinary, bowel, sexual, and hormonal domains. ANOVA tests were performed to compare the means of utilities among severity groups of severity defined by EPIC items (severe, small or no relevant problem). Effect sizes between extreme groups were calculated to estimate the magnitude of differences. RESULTS Mean age was 66.8 years (SD=6.4) at prostate cancer diagnosis, 20.4% were treated with radical prostatectomy, 33.3% with brachytherapy, 26.7% with external radiotherapy, and 19.6% with combined radiotherapy. The utilities indirectly obtained ranged 0.83-0.99 with PORPUS-U and 0.61-0.84 with SF-6D. Both instruments showed significant differences according to problem severity of all domains measured with EPIC (p<0.001). Utilities for patients without problems were higher than patients with severe problems. The effect sizes between the extreme groups with PORPUS-U and SF-6D were: 1.23 and 1.24 for urinary; 1.03 and 0.75 for bowel; 0.98 and 0.96 for sexual; and 0.94 and 2.17 for hormonal domains. CONCLUSIONS Our results suggest that both the generic index SF-6D and the disease-specific index PORPUS-U discriminated adequately the problems related to prostate cancer and their treatments.