BACKGROUND The aim of the study was to assess the safety and efficacy of ultrasound (US)-guided percutaneous nephrolithotomy (PCNL) for complex renal stones when performed in a modified supine position. METHODS We retrospectively reviewed the charts of patients who underwent PCNL for complex renal stones at our institution between August 2018 and December 2021. During this time, 188 consecutive patients underwent US-guided PCNL in the prone position (P group, n = 129) or in the flank-free modified supine position (S group, n = 59). Patient demographics and intraoperative and postoperative data were analyzed. RESULTS Successful renal access was achieved in all patients. The baseline demographics were comparable between the two groups. The numbers of renal access were significantly higher (2.1 ± 0.4 vs. 1.2 ± 0.2, p = 0.002), and the operation time was comparable (79.1 ± 14.6 min vs. 96.2 ± 19.6 min, p = 0.06) between the two groups. The postoperative hospital stay was also shorter in the P group (6.2 ± 1.5 d vs. 10.2 ± 1.7 d, p = 0.008). The postoperative hemoglobin loss was similar between the P and S groups (1.7 ± 0.4 g/dL vs. 1.8 ± 0.3 g/dL, p = 0.12). The stone-free rate was significantly lower in the S group (57.5% vs. 82.7%, p < 0.001). There were no embolization or septic complications. Twelve patients (20.3%) in the S group underwent simultaneous or staged retrograde flexible ureteroscopy to remove residual stones. CONCLUSIONS US-guided PCNL in the modified supine position was a safe treatment for complex renal stones. However, the single-session stone clearance rate was not ideal. The supine flank-free position may be unsuitable for US-guided PCNL in patients with complex renal stones according to our preliminary findings.