Background: This study investigates the impact of United States Preventive Services Task Force (USPSTF) guideline changes regarding prostate specific antigen (PSA) based screening for prostate cancer (PCa) on prostate biopsy outcomes and costs of care in a population of underserved men. Methods: Data were abstracted from male subjects ≥ 50years old who had a prostate biopsy and were part of the Inland Empire Health Plan. After reviewing data from 935 subjects, complete data were obtained from 580 subjects (430 subjects who had a biopsy after the guideline change and 130 who had biopsy before the guideline change). Direct medical cost of cancer care were obtained through claims data (Pharmacy, Professional and Institutional Claims) and were calculated for each member based on the services they had received. Results: Although PSA at time of prostate biopsy was not statistically different between the post and pre guideline subjects (Mean(SD), ng/ml: 6.3(6.2) vs 6.7(7.7), p = 0.73), the risk of being diagnosed with PCa as well as the risk of being diagnosed with high grade disease (Gleason score ≥ 7) was higher in the post guideline group as compared to the pre-guideline group (37.0% vs 30.7% (p = 0.11) and 75.5% vs 56.5% (p = 0.01) respectively). Results from logistic regression (adjusted for age, PSA and race) indicate that the odds of being diagnosed with high grade PCa amongst the subjects that had prostate biopsy after the guideline change was 2.8 times higher as compared to those subjects who had prostate biopsy before the guideline change (Odds ratio and 95% Confidence intervals: 2.8(1.30, 6.07)). Direct medical cost of care for PCa has increased by 78% in the post guideline change era as compared to those prior to the guideline change ($13,292.03 per subject as compared to $7,484.87 per subject respectively). Conclusions: Changes in USPSTF guidelines are associated with higher grade of disease at biopsy as well as cost of care. This could potentially be due to delay in the diagnosis due to lack of PSA screening leading to disease progression. Not only are these results concerning because of its magnitude but also because it has occurred in a short span of 3 years.