Background: Bone is the most frequent site of metastasis in prostate cancer. Accurate localization of recurrence following primary treatment can help optimize salvage therapy. Positron emission tomography (PET) tracer, ¹⁸F-fluciclovine, is approved in Europe and the US for men with rising prostate specific antigen (PSA) after prior treatment. LOCATE was a prospective trial to study the impact of ¹⁸F-fluciclovine PET/computed tomography (PET/CT) on management of men with prostate cancer recurrence and negative standard imaging after curative intent treatment. Here, we explore changes in management (CIM) in men with ¹⁸F-fluciclovine-avid bone lesions. Methods:¹⁸F-Fluciclovine PET/CT was performed and interpreted according to standard practice at 15 US centers. Eligible men (≥ 18 y; prior curative intent treatment of prostate cancer; recurrence based on rising PSA; negative/equivocal findings on standard bone and pelvic imaging) had their treatment plans recorded pre- and post-scan. Results: A total of 213 men (median pre-scan PSA, 1.0 ng/mL) were enrolled. Overall, ¹⁸F-fluciclovine detected lesions in 122 (57%) and 126 (59%) had CIM post-scan. ¹⁸F-Fluciclovine-avid bone lesions were found in 23 (11%) men. Prior to the fluciclovine scan, 21 (91%) had a ^99mTc-MDP scan (20 negative, 1 equivocal results), 1 (4%) had an unspecified bone scan (negative result) and 1 (4%) did not receive a bone-specific scan. Of the 23 men with positive scans, 15 (65%) had post-scan CIM: ADT added to planned radiotherapy (RT; 4, 27%); ADT replaced with targeted treatment of fluciclovine-positive extrapelvic bony areas (4, 27%); RT modified to target fluciclovine-positive areas (4, 27%); modified ADT regime (2, 13%); and watchful waiting in favor of RT (1, 7%). The majority of men with no post-scan CIM were prescribed ADT (6/8, 75%). Conclusions: Despite negative standard bone imaging,¹⁸F-fluciclovine localized recurrence of prostate cancer to bone in 11% of patients; the majority of whom had a management change as a result, frequently in order to target fluciclovine-positive sites. Further study to investigate the clinical outcomes of such changes is warranted. Clinical trial information: NCT02680041