Background: Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients with impact on defintion of subsequent therapies. The use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) presents better accuracy than standard imaging practice. This phase3, prospective, multicentric, international study evaluates the diagnostic performance and clinical impact of PSMA-PET/CT in evaluating BCR in PCa. Methods: Patients with PCa who have undergone primary definitive treatment and with rising PSA were recruited in the study. Overall 17 centers from 15 countries (Azerbaijan, Brazil, Colombia, India, Israel, Italy, Jordan, Lebanon, Malaysia, Mexico, Pakistan, Poland, South Africa, Turkey, and Uruguay) were involved. Images and data were centrally reviewed; data were collected for PSMA site of findings, positivity rate, defined as the percentage of patients with a positive 68Ga-PSMA PET/CT taking into account the composite standard: pathology, correlative imaging, PSA response, with at least 6 mo. clinical follow-up, and impact on patient management by determining changes in the treating physician’s documented clinical plans before and after 68Ga-PSMA PET/CT. Results: Were enrolled 1198 patients and presented final data from 1004 patients. 68Ga-PSMA PET/CT was positive in 654/1004 patients (65.1%); lesions were identified as: prostate/prostatic bed only in 13.7% cases; pelvic lymph nodes only 20.5%, and with any metastatic disease in 27.0%. There was a correlation between PSMA-PET/CT positivity and Gleason score (p<0.001): detection rate was 371/613 (60.5%) in patients with Gleason 7, 130/196 (66.3%) in Gleason 8, 140/180 (77.8%) in Gleason 9 and 13/15 (86.7%) in Gleason 10. There was also significant correlation between lesions identification and PSA values (p<0.001): detection rate was 21/41 (51.2%) for PSA <0.2, 84/188 (44.7%) for PSA between 0.2-0.5, 124/232 (53.4%) for PSA 0.5-1.0, 158/235 (67.2%) for PSA ≥1 and <2, 171/206 (83.0%) for PSA ≥2 and <4, and 96/102 (94,1%) in PSA 4 to 10. Also, treatment was modified based on PSMA results in 56.8% of patients. The 68Ga-PSMA PET/CT positivity was consistent and not statistically different among the countries. Conclusions: This is the largest multicenter trial on 68Ga-PSMA PET/CT detected local and metastatic recurrence in most men with BCR. 68Ga-PSMA PET/CT results changed the recommended treatment approaches in the majority of patients. This study confirms the reliability of PSMA PET in BC and the worldwide feasibility of such approach.