BACKGROUND Percutaneous nephrolithotomy (PCNL) has been widely used in the clinical practice of urinary calculi. The prone positioning for PCNL is generally adopted, while it is associated with a certain risk when repositioning the patient into the prone position after anesthesia. This approach is more difficult for obese or elderly patients with respiratory diseases. The application of PCNL combined with B-mode ultrasound-guided renal access in the lateral decubitus flank position for complex renal calculi has been poorly investigated. This study aimed to evaluate the efficacy and safety of PCNL combined with B-mode ultrasound-guided renal access in the lateral decubitus flank position for complex renal calculi. METHODS From June 2012 to August 2020, 660 patients with renal stones (>20 mm) were enrolled. All patients were diagnosed by ultrasonography, kidney-ureter-bladder (KUB) plain X-ray imaging, intravenous urography (IVU), or computed tomographic urography (CTU). All the enrolled subjects underwent PCNL combined with B-mode ultrasound-guided renal access in the lateral decubitus flank position. RESULTS Successful access was achieved in 660 patients (100%). Micro-channel PCNL and PCNL were performed on 503 and 157 patients, respectively. The stone-free rate was 85.30% (563/660). A dual-channel access was required for phase I PCNL in 92 cases, and reconstruction of channel was required for 33 cases for phase II PCNL. The stone-free rate of phase I PCNL was 85.30% (563/660). Totally, 45 patients had stones that were cleared during phase II PCNL, while 5 patients became stone-free after phase III PCNL. Besides, 12 cases became stone-free after undergoing PCNL combined with extracorporeal shock wave lithotripsy. The mean operation time was 66 (range, 38 to 155) min, and the mean length of hospital stay was 16 (range, 8 to 33) days. One case developed heavy bleeding 6 days after the removal of kidney fistula, and one case developed acute left epididymitis during urethral catheter retention. No visceral injuries and other complications occurred. CONCLUSIONS PCNL combined with B-mode ultrasound-guided renal access in the lateral decubitus flank position is safe and convenient, preventing the surgical team and patients from exposure to harmful radiations.