Supine percutaneous nephrolithotomy (sPCNL) has gained traction in recent years, offering advantages over traditional prone positioning, including reduced anesthesia requirements and simplified access for retrograde instrumentation. This study aimed to evaluate the safety and efficacy of anterior versus posterior calyceal access during sPCNL, particularly given that anterior puncture is rarely performed in prone PCNL due to concerns about renal trauma and limited access to the collecting system. A total of 100 patients undergoing sPCNL with ultrasound-guided access were enrolled, with access location left to the surgeon’s discretion. Among these patients, 76 underwent anterior access while 24 had posterior access. The demographic characteristics, including age, BMI, gender, and preoperative conditions, showed no significant differences between the two groups. Intraoperative metrics such as needlestick attempts, access time, and fluoroscopy duration were similar across both access types, with no recorded visceral or pleural injuries. Importantly, postoperative outcomes, including transfusion rates, stone-free rates, complications within 30 days, and rates of emergency department visits or readmissions, were comparable between the anterior and posterior access groups. The findings suggest that anterior calyceal access during sPCNL can be performed safely and effectively, with over 75% of surgeons preferring this approach. These results support the viability of anterior access as an alternative to posterior entry, indicating that it can be equally effective without compromising patient safety.