To investigate the factors predicting scan positivity and disease location in patients with biochemical relapse (BCR) prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen (PSMA)-targeted F-DCFPyL-PET/CT. This is a two-institution study including 245 BCR PCa patients after primary local therapy and negative conventional imaging. Patients underwent F-DCFPyL-PET/CT. Lesion detection rate and disease location were correlated with patient's tumor characteristics, time from the initial therapy, prostate-specific-antigen (PSA) and PSA doubling time (PSAdt). Multivariate logistic regression analyses were used to determine predictors of a positive scan. Regression-based coefficients were used to develop nomograms predicting scan positivity and extra-pelvic disease. Overall, 79.2% (194/245) of patients had a positive F-DCFPyL-PET/CT, with detection rates of 48.2% (27/56), 74.3% (26/35), 84% (37/44), 96.7% (59/61) and 91.8% (45/49) for PSA <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0 and ≥5.0 ng/mL, respectively. Patients with lesions confined to the pelvis had lower PSAs than those with distant sites (1.6±3.5 vs. 3.0±6.3 ng/mL, p<0.001). In patients treated with prostatectomy ( = 195), 24.1% (47/195) had a negative scan, 46.1% (90/195) showed intra-pelvic disease and 29.7% (58/195) extra-pelvic disease. In the post-radiation subgroup ( = 50), F-DCFPyL-PET/CTs were always negative at PSA lower than 1.0 ng/mL and extra-pelvic disease was seen only when PSA >2.0 ng/mL. At multivariate analysis, PSA, PSAdt were independent predictive factors of scan positivity and the presence of extra-pelvic disease in post-surgical patients, with area under the curve (AUC) of 78% and 76%, respectively. PSA and PSAdt were independent predictors of the presence of extra-pelvic disease in the post-radiation cohort, with AUC of 85%. Time from treatment to scan was significantly longer for prostatectomy-bed-only recurrences than for those with bone or visceral disease (6.2±6.4 vs. 2.4±1.3 years, p<0.001). F-DCFPyL-PET/CT offers high detection rates in BCR PCa patients. PSA and PSAdt are able to predict scan positivity and disease location. Furthermore, the presence of bone/visceral lesions are associated with shorter intervals from treatment compared to prostate-bed-only recurrences. These tools might guide clinicians to select the most suitable candidates for F-DCFPyL-PET/CT imaging.