Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on 68Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of 68Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Methods: Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent 68Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUVmax; and ratio of lesion SUVmax to liver, blood pool, and background bone SUVmax Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Results: Among 56 participants, 13 (22.8%) had false-positive osseous 68Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous 68Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant (P < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUVmax of at least 4.1, and SUVmax ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based 68Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. Conclusion: PSMA RADS rating, SUVmax, and SUVmax ratio for lesion to blood pool can help differentiate benign from malignant lesions on 68Ga-PSMA-11 PET. An SUVmax ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on 68Ga-PSMA-11 PET/MRI and PET/CT.