Background and objective: Micro-ultrasound (micro-US) is a novel imaging modality with diagnostic accuracy comparable to MRI for detecting clinically significant prostate cancer (csPCa). We investigated whether artificial intelligence (AI) interpretation of micro-US can outperform clinical screening methods using PSA and digital rectal examination (DRE). Methods: We retrospectively studied 145 men who underwent micro-US guided biopsy (79 with csPCa, 66 without). A self-supervised convolutional autoencoder was used to extract deep image features from 2D micro-US slices. Random forest classifiers were trained using five-fold cross-validation to predict csPCa at the slice level. Patients were classified as csPCa-positive if 88 or more consecutive slices were predicted positive. Model performance was compared with a classifier using PSA, DRE, prostate volume, and age. Key findings and limitations: The AI-based micro-US model and clinical screening model achieved AUROCs of 0.871 and 0.753, respectively. At a fixed threshold, the micro-US model achieved 92.5% sensitivity and 68.1% specificity, while the clinical model showed 96.2% sensitivity but only 27.3% specificity. Limitations include a retrospective single-center design and lack of external validation. Conclusions and clinical implications: AI-interpreted micro-US improves specificity while maintaining high sensitivity for csPCa detection. This method may reduce unnecessary biopsies and serve as a low-cost alternative to PSA-based screening. Patient summary: We developed an AI system to analyze prostate micro-ultrasound images. It outperformed PSA and DRE in detecting aggressive cancer and may help avoid unnecessary biopsies.