Introduction: The procedure of percutaneous nephrolithotomy (PCNL) is considered a minimally invasive method for removing stones from the kidneys or ureters. PCNL can cause a wide range of complications, such as urosepsis, a rare but serious complication.Methods: A retrospective cohort study of patients who underwent PCNL from the period 2016 to 2022 was conducted at King Abdulaziz Medical City. Data were collected by chart review using the BestCARE system. SPSS version 23 (IBM Corporation, Armonk, NY, USA) was used. Qualitative variables were expressed as percentages and frequencies. The chi-square test was used to compare the qualitative variables. The K-S test was used to check the normality of the data. Quantitative variables were compared between groups using the independent sample t-test and the nonparametric Mann-Whitney test. Fisher's exact test was used to compare categorical variables.Results: A total of 155 patients were included in this study. The mean age of the participants overall was found to be 49. About 108 (69.7%) of the participants were male. Regarding risk factors for urosepsis, diabetes mellitus was found in 54 (34.8%) of the participants. The incidence of urosepsis following PCNL was found to be 3 (1.9%) of the patients. The most frequently reported indication was found to be unilateral renal stones. The most frequently reported type of stone in the analysis was found to be calcium oxalate in nearly two-thirds 98 (63.2%) of the patients.Conclusion: The incidence of urosepsis among the patients who underwent PCNL was less than 2%. Diabetes mellitus, followed by hypertension, were the most prevalent co-morbidities among the participants. Cefuroxime was the antibiotic of choice when treating patients and following urosepsis.