BACKGROUND Serum prostate-specific antigen (PSA) is expected to be undetectable after radical prostatectomy unless there is residual disease or disease progression. The aim of this study was to confirm the usefulness of serum PSA measurements in monitoring patients after radical prostatectomy. METHODS We conducted a study of 50 patients who underwent radical prostatectomy for clinical stage T1-2 or small T3 prostate cancer, analyzed serum PSA levels before and after surgery and compared the pathological findings and clinical outcome. RESULTS Postoperative PSA elevation (PSA failure) was noted in 13% of patients with organ-confined disease (OCD), 43% with positive surgical margins and/or seminal vesicle involvement (PSM/SVI), and 60% with positive lymph nodes (N+). Postoperative clinical failure was noted in 8 patients, and all were preceded by PSA failures. The 3-year PSA failure-free rates were 86.5%, 32.1%, and 40.7% and the 3-year clinical failure-free rates were 100%, 67.5%, and 73.5% in patients with OCD, PSM/SVI and N+, respectively. CONCLUSIONS An elevation of serum PSA levels after radical prostatectomy was a sensitive indicator of persistent disease after surgery, and preceded clinical manifestations of disease progression.