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Radiation therapy (RT) after radical prostatectomy (RP) has been associated with a survival benefit in both the adjuvant and salvage setting. Nevertheless, optimal targeting of the prostate bed following surgery remains challenging. The Calypso 4D Localization System (Calypso Medical Technologies, Seattle, WA, USA) is a target positioning device that continuously monitors the location of three implantable electromagnetic transponders. We describe our technique of ultrasound-guided placement of these transponders into the prostate bed for adjuvant and salvage RT.Seventeen patients presenting to Fox Chase Cancer Center for postoperative RT underwent transrectal ultrasound-guided placement of Calypso beacons. The three transponders were placed approximately 1 cm apart in a triangular fashion around the vesico-urethral anastomosis and in the retrovesicular tissue.All patients were successfully implanted without periprocedural complications. Appropriate beacon position was confirmed by CT scan performed at the time of RT simulation. Intensity-modulated radiation therapy was delivered at a dose of 68 Gy (range 64-68). Treatment was well-tolerated with no Grade 3 or 4 toxicities. Grade2 enteritis was not observed, and there were no cases of rectal bleeding. Genitourinary toxicity was noted in 10 patients and consisted of Grade 1 and 2 frequency and dysuria. No patient developed gross hematuria or urinary retention. All patients (9/9) with at least 6 months of follow up after treatment had an undetectable PSA.The placement of Calypso transponders for adjuvant/salvage RT is a safe and efficacious method for treatment targeting with an acceptable acute toxicity profile.