Background: Burkholderia cepacia, a Gram-negative bacterium within the Burkholderia cepacia complex (BCC), is notorious for its antibiotic resistance and potential to cause severe nosocomial infections. This pathogen poses significant challenges in hospital settings, particularly in urology and following endourological procedures, due to its biofilm-forming ability and environmental resilience. Objective: This study aimed to evaluate the prevalence, impact, and antibiotic sensitivity of B. cepacia infections among patients at the urology clinic of CNHU HKM in Benin over a 36-month period. Methods: A retrospective and prospective cross-sectional study was conducted from January 2022 to June 2024, involving 69 patients infected with B. cepacia. Data collection focused on patient demographics, surgical history, microbiological culture results, antibiotic use, treatment duration, and clinical outcomes. Results: Out of 711 hospitalized patients, 310 were infected (43%), with 69 cases (9.7%) identified as B. cepacia. The average patient age was 61 years. The infection was detected in 57% of patients upon admission and 43% post-operatively. Antibiotic sensitivity tests showed effectiveness to meropenem (62%), ceftazidime (65%), and cotrimoxazole (78%). Recurrence rates were 21% with meropenem, 5% with cotrimoxazole, and no recurrences with a combination of meropenem and cotrimoxazole over 6 months. The average cost of antibiotic therapy was 112 USD, with an average hospital stay of 16 days and a 51.3% recurrence rate in treated patients. Conclusion: Burkholderia cepacia is a multidrug-resistant pathogen that complicates the treatment of urinary and pulmonary infections, particularly after endoscopic procedures. Effective management requires targeted antibiotic therapy and adherence to strict disinfection protocols. The combination of meropenem and cotrimoxazole proved effective, with no recurrences observed in the study period.