We examined the difference in prostate-specific antigen (PSA)-freedom from recurrence (FFR) in patients with localized prostate cancer treated with permanent prostate brachytherapy (PPB) alone or external radiotherapy combined with PPB (RT-PPB). A total of 1476 patients with prostate cancer (T1/T2) were treated with PPB by following the American Brachytherapy Society criteria. Patient self-selection and preference allowed for an overlap of treatment methodologies and risk factors. Monotherapy consisted of 125I or 103Pd. RT-PPB consisted of RT followed by PPB. PSA-FFR was based on a published modification of the American Society for Therapeutic Radiology and Oncology definition. Cox regression analysis was performed to assess the role of Gleason sum, pretreatment PSA value, clinical stage, RT-PPB, the addition of hormones, and the minimum dose covering 90% of the prostate volume (D90 dose). Monotherapy was used for 1016 patients (79%), and RT-PPB was used for 281 patients (21%), with an overall 6-year PSA-FFR of 83.2% (median follow-up of 34.7 months; range, 6-91 months). Multivariate Cox regression analysis to predict PSA-FFR identified the following highly significant variables: pretreatment PSA value, Gleason sum, and the addition of hormones. When the D90% (D90 dose relative to the prescribed dose) was included as a variable, Cox regression identified only the following significant variables: D90%, pretreatment PSA, and Gleason sum. Cox regression failed to identify an improvement in PSA-FFR with RT-PPB or the addition of hormones. Although these conclusions question the role for RT-PPB, only a comparative trial will be able to answer this question definitively.