Objective: Bleeding is one of the most common and alarming complication of percutaneous nephrolithotomy (PCNL). In this study, we aimed to compare the effects of ciprofloxacin and cefuroxime on the bleeding in PCNL procedures. Methods: The study was a retrospective analysis of 97 patients who underwent PCNL between February 2011 and June 2017. We just included the patients who had single tract lower pole PCNL for more objective evaluation of bleeding in the study. The patients were divided into two groups as ciprofloxacin group (Group-I, n:40) and cefuroxime group (Group-II, n:56) according to the type of antibiotic used in the operation. Patient age, gender, body mass index, stone size, preoperative INR, preoperative and postoperative platelet counts and difference, operative time, need for blood transfusion, postoperative fever, hospital stay, postoperative hemoglobin and hematocrit drop were analyzed. Results: There was no statistically significant difference in patients' gender distribution, body mass index, preoperative INR, preoperative and postoperative platelet counts, preoperative and postoperative platelet difference, duration of operation, hospital stay, postoperative fever and need for postoperative blood transfusion between two antibiotic groups (p > 0.05). Mean patient age was 42,75±16,97 in Group-I and 35,54±14,71 in Group-II (p < 0.05). The mean stone size of Group-I and Group-II were 27,23±7,05 mm and 30,59±8,20, respectively (p < 0.05). The mean postoperative hemoglobin and hematocrit drop were significantly higher in Group-I than in Group-II. The mean hemoglobin drop was 1,73±0,95 for Group-I and 1,28±0,67 for Group-II (p < 0.05). The mean hematocrit drop was 5,17±2,76 for Group-I and 3,80±1,99 for Group-II (p < 0.05). Conclusion: On the basis of the results of the initial study, the antibiotic preference in patients undergoing surgery may be one of the bleeding factors during and after PCNL.