Background There is limited published evidence regarding the incidence of intraoperative and postoperative events and the effect of percutaneous nephrolithotomy (PCNL) in supine and prone positions and laparoscopic pyelolithotomy on kidney function in patients with large and complex calculi. Materials and methods We evaluated the surgical outcomes of 97 patients with large and complex kidney stones. The patients were divided into 3 groups: those who underwent PCNL in the prone position, PCNL in the supine position, and pyelolithotomy by laparoscopy and retroperitoneoscopy. General surgical outcomes, size of residual stones, stone-free rate, glomerular filtration rate (GFR), and split GFR obtained from Tc-99m renal dynamic scintigrams were analyzed. Results Percutaneous nephrolithotomy in the prone position was correlated with improved function of the affected kidney. In the supine PCNL group, none of the analyzed indicators demonstrated a significant difference. Dynamic nephroscintigrams revealed negative changes in terms of accumulation and secretion of the affected kidney. A slight decrease in creatinine clearance was noted. However, positive dynamics in split GFR and secretory index were seen in this group. The laparoscopic group showed positive results in all analyzed parameters. However, full assessment of the function of the affected kidney in this group was limited due to restricted use of laparoscopic pyelolithotomy for complex stones. Conclusions Percutaneous nephrolithotomy in the prone position resulted in the most favorable renal functional outcomes for patients with high-grade renal calculi, whereas a laparoscopic approach may be preferred for patients with stones of lower grades. The most significant factors that adversely affected renal function were intraoperative bleeding volume, kidney stone size and density, and body mass index.