Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used for primary staging in prostate cancer (PC), mainly because of its improved accuracy in detecting lymph node metastases compared with conventional imaging. However, the diagnostic benefit of PSMA PET/CT for detecting bone metastases is less well established. This study compares the diagnostic accuracy of 18F-PSMA PET/CT and 18F-NaF PET/CT for detecting bone metastases in patients newly diagnosed with PC. Methods: This prospective study included patients with histologically confirmed high-risk PC. All participants were referred from the department of urology to 18F-NaF PET/CT and underwent 18F-PSMA PET/CT within 3 weeks. Images were reviewed by 2 nuclear medicine physicians unaware of the results of the other imaging modality. Presence or absence of bone metastases and number of metastatic lesions were recorded. A reference standard was established at the patient level based on agreement between the 2 imaging modalities. In cases of concordance, both modalities were deemed correct. In cases of discordance, additional follow-up scans were performed. Diagnostic performance metrics, including sensitivity, specificity, and accuracy, were calculated. Results: In total, 160 participants were included. Sensitivity, specificity, and accuracy for detecting bone metastases at the patient level were 0.98, 0.99, and 0.99, respectively, for 18F-PSMA PET/CT, and 0.91, 1.00, and 0.97, respectively, for 18F-NaF PET/CT. No significant differences were found. The concordance rate of bone metastases between 18F-NaF and 18F-PSMA PET/CT at the patient level was observed in 154 patients (96.3%). 18F-PSMA PET/CT tended to identify more bone metastases per patient than 18F-NaF PET/CT. Conclusion: Both 18F-NaF and 18F-PSMA PET/CT exhibit high diagnostic accuracy for detecting bone metastases in newly diagnosed high-risk PC patients. 18F-PSMA PET/CT may detect additional metastatic lesions compared with 18F-NaF PET/CT. Subsequent 18F-NaF PET/CT may be redundant if no bone metastases are found on 18F-PSMA PET/CT.