We examined decisional regret among prostate cancer patients and its association with disease-specific quality of life. Patients (N = 793) completed questionnaires at diagnosis, at 6 months, and 12 months thereafter. Although levels of decisional regret were low, regret increased significantly between 6 and 12 months after diagnosis. The increase was substantial for patients treated with prostatectomy compared to patients treated with external beam radiation or brachytherapy. Cross-sectional, significant, and positive associations among regret, activity limitation attributed to urinary dysfunction, and bother with sexual and urinary dysfunction emerged. Longitudinally, the change in the level of regret was significantly associated with treatment modality and with the change in bother with sexual dysfunction over the first 6 months after diagnosis. Extensive discussions about disease-specific quality of life should be included when physicians counsel patients about treatment options.