Prostate cancer is one of the major causes of cancer death for men in the western world. Magnetic resonance imaging (MRI) is being increasingly used as a modality to detect prostate cancer. Therefore, computer-aided detection of prostate cancer in MRI images has become an active area of research. In this paper we investigate a fully automated computer-aided detection system which consists of two stages. In the first stage, we detect initial candidates using multi-atlas-based prostate segmentation, voxel feature extraction, classification and local maxima detection. The second stage segments the candidate regions and using classification we obtain cancer likelihoods for each candidate. Features represent pharmacokinetic behavior, symmetry and appearance, among others. The system is evaluated on a large consecutive cohort of 347 patients with MR-guided biopsy as the reference standard. This set contained 165 patients with cancer and 182 patients without prostate cancer. Performance evaluation is based on lesion-based free-response receiver operating characteristic curve and patient-based receiver operating characteristic analysis. The system is also compared to the prospective clinical performance of radiologists. Results show a sensitivity of 0.42, 0.75, and 0.89 at 0.1, 1, and 10 false positives per normal case. In clinical workflow the system could potentially be used to improve the sensitivity of the radiologist. At the high specificity reading setting, which is typical in screening situations, the system does not perform significantly different from the radiologist and could be used as an independent second reader instead of a second radiologist. Furthermore, the system has potential in a first-reader setting.