OBJECTIVE To compare the safety and effectiveness of flexible ureteroscopy (F-URS) with transperitoneal laparoscopic ureterolithotomy (TPLU) in cases of obstructive pyelonephritis secondary to large proximal ureteral stones. METHODS A series of 42 patients presenting with obstructive pyelonephritis due to proximal ureteral stones larger than 1.5 cm were included from April 2006 to February 2015 in this comparative study. After drainage of pyonephrosis and resolution of sepsis, 22 patients treated with TPLU (Group I), and 20 patients were treated with F-URS (Group II). Preoperative patient and stone characteristics, procedure-related parameters and clinical outcomes were assessed for each group. RESULTS It was seen that both methods were effective in the treatment of large proximal ureteral stones. However TPLU provided a higher stone- free rate (100% vs 80%. p=0.043) and lower retreatment rate. There was no difference between the groups for the operative time and complication rate. On the other hand, patients treated with F-URS had less postoperative pain (p=0.008), a shorter hospital stay (p<0.001) and a faster return to daily activities (p<0.001). CONCLUSIONS The results of our study show that both F-URS and TPLU are safe and effective surgical procedures for treatment of large proximal ureteral stones after controlling obstructive pyelonephritis. However, TPLU has a higher stone-free rate with comparable operating time and complication rate as compared to F-URS. On the other hand F-URS has the advantages of less postoperative pain, shorter hospital stay and faster return to daily activities.