Objectives <p>Hem-o-Lok clips and endovascular staplers are the most commonly used methods for vascular ligation in laparoscopic nephrectomy procedures. This study aimed to compare the effect of Hem-o-Lok clips and endovascular staplers on surgical and clinical outcomes in laparoscopic nephrectomies performed for various indications.</p> Materials and methods <p>This study included 201 patients who underwent transperitoneal laparoscopic nephrectomy with vascular ligation performed using either Hem-o-Lok clips or endovascular staplers. In addition to evaluating the effect of the vascular ligation method on surgical and clinical outcomes, the study also compared the demographic, surgical, and clinical parameters of patients grouped based on intraoperative blood loss and operation duration.</p> Results <p>There was no significant difference between the groups regarding complication rates, conversion to open surgery, erythrocyte suspension transfusion, length of hospitalization, or pathology results. However, operation duration was significantly longer in the Hem-o-Lok clip group compared to the endovascular stapler group (<i>p</i> &lt; 0.001). In addition, estimated intraoperative blood loss was significantly higher in the Hem-o-Lok clip group (<i>p</i> = 0.006). Logistic regression analysis identified Hem-o-Lok clips as the most significant predictor of increased intraoperative blood loss and prolonged operation duration (<i>p</i> = 0.012, and <i>p</i> = 0.010, respectively).</p> Conclusions <p>Both Hem-o-Lok clips and endovascular staplers are safe and effective options for vascular ligation in laparoscopic nephrectomy. However, the endovascular stapler method offers advantages in terms of reduced operation duration and lower intraoperative blood loss. Factors such as operation duration, risk of blood loss, device cost, and surgeon experience should be taken into consideration when selecting a vascular ligation method.</p>