Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA ≤ 10, Gleason ≤ 6) from Kaiser Permanente Northern California. We assessed psychological and decision-making variables, and treatment preference [AS, AT, and No Preference (NP)]. Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. ©2016 AACR.