Abstract Introduction: The aim of this study is to verify the predictive role of transrectal ultrasound (TRUS) of prostatic fossa, digital rectal examination (DRE), prostate specific antigen (PSA) and pathological stage after radical prostectomy in the detection of a prostate tumor recurrence at the level of the vesico-urethral anastomosis by means of multiple TRUS biopsies (6–8 cores). Material and Methods: From October 1997, following a radical prostatectomy, 119 consecutive patients (median age: 67.9 years) with a PSA≥0.2 ng/ml (median PSA: 0.9 ng/ml) underwent DRE and TRUS examinations with a 5.0–7.5 MHz variable frequency end-fire probe (Hitachi Medical System) and an EUB-525 machine. All patients received six TRUS-guided biopsies of the vesico-urethral anastomosis, and 1–2 additional biopsies directed to hypo-echoic or suspicious areas, if detected by TRUS. Results: Biopsies revealed recurrent carcinoma in 50% of patients (60/119). TRUS proved more sensitive than DRE (75% vs. 50%; p=0.01) and, conversely, DRE proved more specific than a TRUS (85% vs. 66%; p=0.03). Cancer was detected in 45% of the 34 patients with a PSA≤0.5 ng/ml. In the group of patients with a PSA≥2.0 ng/ml (24 patients), TRUS was able to detect every biopsy-proven local recurrence lesion (sensitivity: 100%). Conversely, all patients with a PSA≥2.0 ng/ml and a negative TRUS had a negative biopsy (negative predictive value: 100%). In a multi-variable logistical analysis, the most predictive parameters determining a positive biopsy rate among those values studied (PSA, DRE, TRUS, positive surgical margins, pathological stage and time to PSA elevation) were TRUS and DRE findings ( p=0.003, with an odds ratio of 4.6 and p=0.02, with an odds ratio of 4.1, respectively). Conclusion: TRUS and TRUS biopsies utilizing 6–8 cores are efficient tools in the detection of local recurrence after a radical prostatectomy, even with a PSA≤0.5 ng/ml. A combination of TRUS and DRE findings seems to predict biopsy results best. In case of a PSA≥2.0 ng/ml and a negative TRUS, a biopsy of the vesico-urethral anastomosis could be avoided since the negative predictive value is 100%. Cancer recurrence detection seems to be predicted by TRUS and DRE findings, but not by PSA levels, pathological stage, status of the surgical margins or time to PSA elevation.