Numerous observational studies have assessed the clinical predictors of switching from active surveillance (AS) to active treatment (AT), but few have assessed psychological and decisional predictors. In a prospective, comparative effectiveness cohort study of men newly diagnosed with low-risk PCa, we assessed whether psychological and decisional factors predicted switching to AT after adjusting for clinical factors. We conducted pre-treatment telephone interviews ( N = 1,139; 69.3% participation) with low-risk PCa patients (PSA 〈 10, Gleason 〈 7) and a follow-up assessment 6–10 months post-diagnosis ( N = 1057; 93%). Clinical variables were obtained from the medical record. The current analysis included men who were on AS for up to 24 months ( N = 515), compared to men on AS for 〉12 months who switched to AT between 12–24 months ( N = 86). In Cox proportional hazard models, we included 2 time-dependent covariates measured between diagnosis and 24-months post-diagnosis: PSA (〈4, 4–9.99, 10+) and Gleason score (〈7, 7+, no surveillance biopsy). Baseline covariates included age (X = 62.3 (SD = 7.0), first degree relative with PCa (25%), number of positive cores (〈2 = 75%), urologist initial treatment recommendation (14% AT). Covariates measured at 6 months included prostate- specific anxiety, decisional satisfaction, decisional uncertainty, and preference for shared vs. independent decisions. The fully adjusted model indicated that switching to an active treatment was more likely among those with a PSA 〉 10 (HR 5.6, 2.4–13.1), Gleason 7+ (HR 20.2, 12.2–33.4), and the urologist's initial recommendation of AT (HR 2.1, 1.04–4.2). The psychological variables, including preference for making independent treatment decisions (HR 2.7, 1.07–6.9) and concern that disease progression will not be detected (HR 1.5, 0.95–2.4), were independently associated with undergoing AT. After adjusting for clinical evidence of disease progression over the first two years post-diagnosis, men's concerns that disease progression will not be detected and preference for making their own treatment decision each independently predicted undergoing AT. These findings suggest the need to provide information and assistance to men who may be uncertain about remaining on AS, particularly when AS remains clinically indicated.