Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse-free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case-control study between 1995 and 2002. Self-reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI = 1.2-3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06-4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.