Background: In patients with biochemical relapse (BCR) following radical prostatectomy (RadP), risk stratification by clinical indices alone is suboptimal for identifying subgroups likely to benefit from salvage radiotherapy (RT). It is also recommended that combination hormonal therapy (HT)-RT improves rates of salvage and survival, hence the need for a clinical tool to better stratify patients for RT and HT-RT; the latter approach for patients at risk of occult metastases. Herein, we investigated the role of ⁶⁸Ga-Prostate-specific Membrane Antigen (PSMA)-PET in the detection of regional and distal recurrences, and for clinical decision making in a prospective cohort of patients with BCR post-RadP. Methods:⁶⁸Ga-PSMA-PET and CT were performed in a cohort of 50 RadP patients with BCR. Radiological interpretation was independently performed by two assessors, who were blinded to the patient identifiers. PSMA+ lesions were considered as true positives; negative-PSMA in the presence of continued PSA rise defined false negative. Impact on clinical decision making was reviewed by comparison of PSMA-PET and CT findings in the post-RadP PSA 0.5-2.0 ng/ml subgroup. Results: Overall detection rate for ⁶⁸Ga-PSMA/PET was 74% (37 of 50) in our cohort with a median post-RadP PSA level of 2.19 (IQR = 0.45-4.26). Detection rates were significantly increased at a PSA cut-off > 1.0; 96% (25 of 26) at > 2.0 and 100% (5 of 5) at 1.0-2.0 compared to 67% (4 of 6) at 0.5-1.0, and 23% (3 of 13) at < 0.5 (P < 0.001). In 0.5-2.0 PSA subgroup, 3 regional nodes and 11 distal (6 nodes, 4 bones, 1 lung) lesions were detected. This altered treatment in 5 of the 11 (46%) cases; 3 N+ cases would have been recommended for HT-RT and pelvic nodal RT, while RT would be omitted in 2 patients due to low volume systemic disease. Conclusions: Our findings support the existing data for PSMA-PET as a sensitive diagnostic tool for clinical recurrences post-RadP. Additionally, the detection of small volume nodal and distal lesions at post-RadP PSA levels of < 2.0 ng/ml highlights the potential utility of PSMA-PET for selecting patients to treatment intensification with HT-RT or omission of RT in cases of distal relapse.