BACKGROUND: The objective of this study was to create a nomogram model integrating clinical and multiparametric magnetic resonance imaging (MP-MRI)-based variables to predict prostate cancer upgrading in a population of active surveillance (AS) patients. METHODS: Prostate cancer patients on AS who underwent MP-MRI with magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided biopsy were identified. Clinical and imaging variables, including the prostate-specific antigen density (PSAD), number of lesions, total lesion volume, total lesion density, Prostate Imaging Reporting and Data System magnetic resonance imaging suspicion score (MRI-SS), and duration between prereferral systematic and MRI/US fusion-guided biopsy sessions, were assessed. Logistic regression modeling was used to assess upgrading on MRI/US fusion-guided biopsy. A predictive model for upgrading was calculated with the significant factors identified. RESULTS: Seventy-six patients were analyzed with a mean age of 62.5 years and a median prostate-specific antigen (PSA) level of 5.1 ng/mL. The average duration between prereferral and MRI/US biopsies was 21 months. Twenty patients (26.32%) were upgraded. The PSAD, duration between prereferral and MRI/US biopsies, MRI-SS, and MRI total lesion density were significantly associated with upgrading. A logistic regression model using these factors to predict upgrading on confirmatory MRI/US fusion biopsy had an area under the curve (AUC) of 0.84, whereas the AUC was 0.69 with PSA alone. On the basis of this model, a nomogram was generated, and using a probability cutoff of 22% as an indication of upgrading, it produced sensitivity, specificity, positive predictive, and negative predictive values of 80%, 81.25%, 57.1%, and 92.86%, respectively. CONCLUSIONS: The integration of MRI findings with clinical parameters can add value to a model predicting upgrading from a Gleason score of 3 + 3 = 6 in men on AS. This can potentially be used as a noninvasive approach to confirm AS patients with low-risk disease for whom biopsy may be deferred. Cancer 2017;123:1941-1948. © 2017 American Cancer Society.