Multiparametric MRI (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). ⁶⁸Ga-PSMA-11 PET/CT (⁶⁸Ga-PSMA PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intraprostatic PSMA activity, proposing a 5-point PRIMARY score to optimize the accuracy of ⁶⁸Ga-PSMA PET/CT for csPCa in a low-prevalence population. Methods: The PRIMARY trial was a prospective multicenter phase II imaging trial that enrolled men with suspected PCa, no prior biopsy, and a recent mpMRI examination (6 mo) and for whom prostate biopsy was planned. In total, 291 men underwent mpMRI, ⁶⁸Ga-PSMA PET/CT, and systematic biopsy with or without targeted biopsy. The mpMRI was read separately using the Prostate Imaging Reporting and Data System (PI-RADS) (version 2). ⁶⁸Ga-PSMA PET/CT (pelvis only) was acquired a minimum of 60 min after injection. ⁶⁸Ga-PSMA PET/CT was centrally read for pattern (diffuse transition zone [TZ], symmetric central zone [CZ], focal TZ, or focal peripheral zone [PZ]) and intensity (SUV_max). In this post hoc analysis, a 5-level PRIMARY score was assigned on the basis of analysis of the central read: no pattern (score of 1), diffuse TZ or CZ (not focal) (score of 2), focal TZ (score of 3), focal PZ (score of 4), or an SUV_max of at least 12 (score of 5). Two further readers independently assigned a PRIMARY score to 118 scans to determine interrater agreement. Associations between PRIMARY score and csPCa (International Society of Urological Pathology grade group ≥ 2) were evaluated. Results: Of the 291 men enrolled, 162 (56%) had csPCa. A PRIMARY score of 1 was present in 16% (47); a score of 2, in 19% (55); a score of 3, in 10% (29); a score of 4 in 40% (117); and a score of 5, in 15% (43). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117), and 100% (43/43), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for a PRIMARY score of 1 or 2 (low-risk patterns) versus a PRIMARY score of 3-5 (high-risk patterns) were 88%, 64%, 76%, and 81%, respectively, compared with 83%, 53%, 69%, and 72%, respectively, for a PI-RADS score of 2 versus 3-5 on mpMRI. The Cohen κ for a PRIMARY score of 1 of 2 versus a PRIMARY score of 3-5 was 0.76 (95% CI, 0.64-0.88) for reader 1 and 0.64 (95% CI, 0.49-0.78) for reader 2. Conclusion: A PRIMARY score incorporating intraprostatic pattern and intensity on ⁶⁸Ga-PSMA PET/CT shows potential, with high diagnostic accuracy for csPCa. Further validation is warranted before implementation.