Our study aims to evaluate the influence of potential determinants of glomerular filtration rate (GFR) decrease after partial nephrectomy (PN), including renal parenchymal loss and other clinical, tumoral, and surgical factors. Eighty-six patients who had undergone PN and for whom preoperative and postoperative computerized tomography scans were available were selected. We calculated the preoperative total kidney volumes, tumor volumes, and postoperative total kidney volumes 1 year after surgery using a three-dimensional (3D) volume segmentation method. Factors that may be potential determinants of percent GFR decrease were also evaluated, including patient age, type of procedure (laparoscopic vs. open), comorbidity index, preoperative GFR, tumor size and volume, RENAL nephrometry score, warm ischemia time, and 3D calculated renal parenchymal loss. Clinical, surgical, and tumor parameters potentially associated with renal parenchymal loss were evaluated. The mean age of the patients was 58 years, the mean tumor diameter was 3.6 cm, and the mean tumor volume was 11.7 cc. The mean percent of renal parenchymal loss was 22.3%, and the mean percent of GFR loss was 17.3%. The renal parenchymal loss was strongly associated with age (r = 0.702, P = .02), Charlson comorbidities index (r = 0.768, P < .001), and RENAL nephrometry score (r = 0.812, P < .001). In multivariate logistic regression analysis, older age, higher Charlson comorbidities index, higher percent renal parenchymal loss, and higher RENAL nephrometry score were independently associated with higher percent of GFR loss. Of all the factors analyzed, RENAL score and Charlson comorbidities index were the most accurate predictors of postoperative parenchymal loss. Also, the percent decrease in GFR at late time points was associated with renal volume preservation and quality of the remnant parenchyma.