BACKGROUND: The increase in multiparametric magnetic resonance imaging (mpMRI) examinations as a fundamental tool in prostate cancer (PCa) diagnostics raises the need for supportive computer-aided imaging analysis. Therefore, we evaluated the performance of a commercially available AI-based algorithm for prostate cancer detection and classification in a multi-center setting. METHODS: Representative patients with 3T mpMRI between 2017 and 2022 at three different university hospitals were selected. Exams were read according to the PI-RADSv2.1 protocol and then assessed by an AI algorithm. Diagnostic accuracy for PCa of both human and AI readings were calculated using MR-guided ultrasound fusion biopsy as the gold standard. RESULTS: Analysis of 91 patients resulted in 138 target lesions. Median patient age was 67 years (range: 49-82), median PSA at the time of the MRI exam was 8.4 ng/mL (range: 1.47-73.7). Sensitivity and specificity for clinically significant prostate cancer (csPCa, defined as ISUP ≥ 2) were 92%/64% for radiologists vs. 91%/57% for AI detection on patient level and 90%/70% vs. 81%/78% on lesion level, respectively (cut-off PI-RADS ≥ 4). Two cases of csPCa were missed by the AI on patient-level, resulting in a negative predictive value (NPV) of 0.88 at a cut-off of PI-RADS ≥ 3. CONCLUSIONS: AI-augmented lesion detection and scoring proved to be a robust tool in a multi-center setting with sensitivity comparable to the radiologists, even outperforming human reader specificity on both patient and lesion levels at a threshold of PI-RADS ≥3 and a threshold of PI-RADS ≥ 4 on lesion level. In anticipation of refinements of the algorithm and upon further validation, AI-detection could be implemented in the clinical workflow prior to human reading to exclude PCa, thereby drastically improving reading efficiency.