Background: The aim of this study was to validate and compare Guy's and S.T.O.N.E. scoring systems in predicting perioperative and postoperative outcome following percutaneous nephrolithotomy (PCNL). Materials and Methods: From November 2015 to June 2017, 190 patients with renal stones who underwent single tract unilateral PCNL in the prone position were included in our study. Guy's and S.T.O.N.E. nephrolithometry scores were calculated in each case based on preoperative computed tomography images. The association of these scoring systems with stone-free status, length of hospital stay, operative time, and postoperative complications was studied. Regression analysis was done, and receiver operating characteristic curves were plotted. Results: Mean S.T.O.N.E. and Guy's stone scores were 8.76 ± 2.29 and 2.70 ± 1.0, respectively. When compared with patients with residual stones, stone-free (SF) patients had significantly lower mean Guy's score (2.58 ± 1.01 vs. 3.23 ± 0.77 [P < 0.001]) and S.T.O.N.E. scores (8.44 ± 2.24 and 10.17 ± 2.0 [P < 0.001]), respectively. On logistic regression analysis, both Guy's score (odds ratio [OR] = 0.48, P = 0.001) and S.T.O.N.E score (OR = 0.78, P = 0.001) were found to be significantly associated with SF status. Both of these scoring systems were also significantly associated with longer operative time (>90 min), prolonged hospital stay (>3 days) and overall complications. No significant difference was found in the area under curve for both scoring systems for stone clearance. Conclusion: Both the S.T.O.N.E and Guy's scoring systems were found to predict the outcome of PCNL, either of these could be used in the routine clinical practice for patients' counseling.