Purpose: Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. Patients and Methods: PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. Results: Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05). Conclusion: This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.