PURPOSE: False-positive screening tests may induce persistent psychological distress despite the absence of disease. The aim of this study is to determine whether a positive screening test (abnormal PSA or digital rectal exam) without biopsy evidence of prostate cancer (PCa) is associated with differences in quality of life and health perceptions during short-term follow-up. METHODS: We conducted a cross-sectional telephone survey of two groups of men approximately two months after testing: 1) Cases: 109 men with an abnormal screening test (without biopsy evidence of PCa), and 2) Controls: 101 age-matched primary care patients who received PSA screening (with a normal result, <4 ng/ml). Primary outcomes included mental health and role-emotional function (SF-36), state anxiety (SAI6), and PCa-related worry. Secondary outcomes sexual function/bother. Outcomes were compared using the Wilcoxon rank-sum test; ordinal logistic regression was used to adjust for residual differences in baseline covariates. RESULTS: Cases and controls were similar across demographic characteristics, medical comorbidity, history of depression/anxiety, and urinary function (based on the AUA score). There were no significant differences across SF-36 subscales or state anxiety. Cases were more worried about PCa despite having a negative prostate biopsy: median worry=4 vs. 5, p=.0001 (where 1=extreme and 5=not at all). In addition, 31% of cases and 11% of controls believed that they had a moderate-high likelihood (>1 in 10) of developing prostate cancer within 5 years (p=.0003). Cases also reported more bother with sexual function than controls: median bother=2 vs. 1, p=.0001 (where 1=no problem and 5=big problem). CONCLUSION: Men with false positive PCa screening tests do not demonstrate significantly worsened psychological or role functioning after learning their biopsy results. Clinicians and policymakers should recognize, however, that false positive screening tests may be associated with heightened sense of susceptibility to PCa and more bother with sexual function. These findings call attention to the need for effective education and counseling interventions prior to PCa screening and during follow-up (for those men with abnormal screening tests).