Purpose: Conventional imaging rarely localizes the site(s) of prostate cancer recurrence in patients undergoing evaluation for salvage radiation therapy (sRT) after radical prostatectomy (RP). LOCATE (NCT02680041) was a prospective, multicenter study investigating the impact of 18F-fluciclovine positron emission tomography and computed tomography (PET/CT) on the management of patients with biochemical recurrence of prostate cancer after curative-intent radiation or RP and negative or equivocal conventional imaging. Our objective was to determine the impact of 18F-fluciclovine PET/CT on treatment decisions for men planning to undergo sRT for biochemical recurrence post-RP. Methods and Materials: We conducted a subgroup analysis of post-RP patients enrolled in LOCATE who were planning to undergo sRT with or without hormonal therapy based on prescan documentation. 18F-Fluciclovine PET/CT was performed according to standardized procedures. The treatment plan postscan was compared with the prescan plan, and Fisher exact test was used to determine the impact of prescan prostate-specific antigen (PSA) and Gleason sum (GS) on positivity and anatomic patterns of uptake. Results: A total of 114 patients (median prescan PSA 0.42 [interquartile range, 0.3-1.1] ng/mL) met selection criteria (54% of patients in LOCATE). Forty-eight (42%) had 18F-fluciclovine-avid lesions. Twelve patients (11%) had positive findings only in the prostate bed, 24 (21%) had positivity only in the pelvis (prostate bed or pelvic nodes), and 24 (21%) had extrapelvic findings. PSA >0.5 ng/mL and GS ≥8 were associated with a higher risk of extrapelvic positivity (P < .05). Postscan, 55 (48%) patients had a management change; 37 (32%) had a change in overall treatment approach (ie, omission of sRT); and 18 (16%) had sRT target modification. Conclusions: 18F-Fluciclovine PET/CT is positive in nearly half of patients planning to undergo post-RP sRT with negative/equivocal conventional imaging, with findings frequently leading to changes in management. PSA >0.5 ng/mL and GS ≥8 are associated with a higher risk of extrapelvic positive findings.