Objectives: Acute obstructive pyelonephritis (AOP) is a urological emergency that combines bacterial infection with upper urinary tract obstruction. This retrospective study focuses on the microbial etiology and causes of obstruction, clinical manifesta-tions, antibacterial therapy, drainage type, and outcomes in patients diagnosed with AOP at a tertiary urology center between 1 January 2020 and 30 December 2024. Methods: One hundred patients with a mean age of 61.30 years were included in this retrospective study, which examines demographic data, comorbidities, clinical fea-tures, pathogens involved, antimicrobial regimens, and hospital outcomes. Results: Urolithiasis was the most frequent cause of obstruction (62%), followed by ureteral stenosis (14%) and tumors (11%). AOPs were mainly produced by Escherichia coli (58%), followed by Klebsiella spp. (21%); 18% of all identified bacteria were ESBL-producing Gram-negative bacilli, and 29% were MDR bacteria. The most used IV antibiotics were fluoroquinolones (52%), followed by cephalosporins (19%) and carbapenems (18%). Carbapenems were administered to all patients with AOP caused by ESBL-producing pathogens and to 62% of those with MDR bacteria. The duration of antibiotic therapy was individualized based on clinical response. Switch to oral administration was made after 4.3 ± 1.5 days, and the antibiotic treatment lasted 10.8 ± 3.2 days. Conclusions: The present study results support the integration of evidence-based guidelines with regional patterns of bacterial susceptibility to optimize therapeutic approaches and reduce severe outcomes in patients with AOP, most of whom have multiple comorbidities.