To develop a novel nomogram that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings and to compare its predictive accuracy to, respectively: 1) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, 2) Johns Hopkins (JH) criteria, 3) EAU low risk classification and 4) EAU low risk or low volume ISUP GG2 classification. Overall, we selected 1 837 patients with ISUP GG 1 or ISUP GG2 prostate cancer that were treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (csPCa) at RP, defined as: ISUP GG≥3 and/or pT≥3a and/or pN1. First, logistic regression models including PRIAS, JH, EAU low risk and EAU low risk or low volume ISUP GG2 binary classifications (not eligible vs. eligible) were used. Second, a multivariable logistic regression model including age, PSA-D, ISUP GG and the percentage of positive cores (Model 1) was fitted. Third, PI-RADS score (Model 2), extracapsular score (ECE) (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the ROC-curve (AUC), calibration plots and decision-curve analyses were used. Of 1 837 patients, 775 (42.2%) presented csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%) and 209 (11.4%) patients were eligible to AS according to, respectively, low risk classification, low risk or low volume ISUP GG2 classification, PRIAS criteria and JH criteria. The proportion of csPCa among low risk, low risk or low volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had greater AUC (0.84), compared to the four proposed AS criteria (all p<0.001). The adoption of a 25% nomogram threshold increased the proportion of AS eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (∆:-14.3%), JH (∆:-5.9%), low risk (∆:-17.2%) and low risk or low volume ISUP GG2 (∆:-18.0%) classifications. A novel nomogram that combines clinical, biopsy and mpMRI findings is able to increase of approximately 25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, PRIAS or JH criteria. Moreover, this nomogram significantly reduces the estimated frequency of csPCa that would be recommended for AS compared to, respectively, PRIAS, JH, EAU low risk and EAU low volume ISUP GG2 classifications.