This study provides further insights into those preoperative parameters that predict side-specific risk of pathological stage in men undergoing radical prostatectomy (RP). The transrectal ultrasound-guided tissue biopsy cores obtained from the right and left sides of the prostate were collected in separate jars and examined independently according to the side of origin in 1250 men with clinically localized prostate cancer who underwent RP. The side-specific biopsy specimens were examined for Gleason score, number of positive cores, percentage of positive cores, percent tumor volume in the biopsy specimens and the presence of perineural invasion. All of the surgical specimens were processed and analyzed by pathologists at NYUMC using a standardized protocol. The surgical specimens were examined for side-specific extracapsular extension (ECE) and seminal vesicle invasion (SVI). Using a univariate analysis, age, serum prostate-specific antigen (PSA), prostate volume, clinical stage, Gleason score, number of positive biopsies, percent positive biopsy cores, percent volume of prostate cancer in cores and perineural invasion were all significant predictors of both ECE and SVI. A multivariate analysis was performed to determine the independent predictors of ECE and SVI. Serum PSA, biopsy Gleason score, percent volume of biopsy cores with cancer and perineural invasion were independent predictors of side-specific ECE. Age, serum PSA, Gleason score and prostate volume were independent predictors of side-specific SVI. Our study identified previously unrecognized independent predictors of side-specific ECE and SVI. Our study also provides evidence that the independent predictors of ECE and SVI are different.