Aim <p>The sensitivity of PSMA-PET/CT for the detection of recurrent prostate cancer (rPC) is good at low PSA values and rapidly rises to &gt; 80% in patients with PSA &gt; 1.5 ng/mL. Currently, there are no general rules on how to manage PSMA-PET-negative patients with rPC and PSA levels at which a pathological PSMA-PET must be considered very likely. The aim of this evaluation was to assess the value of a choline-PET/CT in such a clinical context.</p> Materials and methods <p>We conducted a retrospective analysis incorporating data from 01/2017–09/2023 from two Swiss institutions. Eligible patients included those with rPC following radical prostatectomy (RP) who had a negative or equivocal [^{6 8} Ga]Ga-PSMA-11 or [^{1 8} F]F-PSMA-1007 PET/CT despite a PSA level ≥1.5 ng/mL, and were subsequently referred for [¹⁸F]F-Fluorocholine-PET/CT within two months. Two experienced nuclear medicine physicians reviewed both scans (choline and PSMA-PET/CTs) in a blinded consensus read.</p> Results <p>Eleven patients met all inclusion criteria. The median PSA level was 2.8 ng/mL (range: 1.7–16.0). Following [¹⁸F]F-Fluorocholine-PET/CT 6 out of 11 patients (54.5%) demonstrated pathologic choline positive findings indicative of rPC: 4 patients with local recurrence, 1 with distant metastasis only, and 1 with concomitant pelvic lymph node and distant metastases.</p> Conclusion <p>More than 50% of patients with a negative or equivocal PSMA-PET/CT showed pathologic [¹⁸F]F-Fluorocholine-PET/CT. These results indicate that [¹⁸F]F-Fluorocholine-PET/CT may serve as a valuable complementary imaging modality in patients with rPC after RP who present with a negative PSMA-PET/CT at PSA levels ≥1.5 ng/mL.</p>