Objective To compare the safety and efficacy of minimally-access percutaneous nephrolithotomy (Mini-PCNL) in modified lateral position and prone position in high-risk patients with upper urinary tract stones and explore the clinical value of the modified lateral position. Methods We retrospectively analyzed 82 cases of high-risk patients underwent ultrasound-guided percutaneous nephrolithotomy from June 2010 to December 2015. 43 cases in group of modified lateral position and 39 case in group of prone position. The mean operating time, the success rate of stone fragmentation, hospitalization days, the value of postoperative hemoglobin decline and complication rate of patients were record and compared between the two groups. Results There was no statistical significance between the modified lateral position group and prone position group (P > 0.05) in gender, age, stone type, BMI, the score of ASA and preoperative complication. There was statistical significance in found access time, (7.88 ± 0.82) min in the modified lateral position group and (8.50 ± 0.80) min in the prone position group (P < 0.01). The stone free rate in the modified lateral position group (95.35 %) was higher than that in prone position group (74.36 %), the value of postoperative hemoglobin decline were (9.33 ± 2.49) g/L and (10.90 ± 3.54) g/L, respectively (P < 0.05); Two groups of the pleural damage rate had significant difference (P < 0.05); the hospitalization days and operating time were no statistical difference between the two groups (P > 0.05). Conclusions The Mini-PCNL in modified lateral position for high-risk patients had advantages of found access time, stone clearance rate, pleural injury, blood loss, comfort degree and security and worthy of clinical promoting.