Acinetobacter baumannii has proven to be an increasingly important and demanding species in health care-associated infections. The drug-resistant nature of the pathogen and its unusual and unpredictable susceptibility patterns make empirical and therapeutic decisions even more difficult. Most of the published and running studies for treatment of multidrug-resistant Acinetobacter baumannii (MDR-AB) depends on the usage of older class of antibiotic (Colistin) either alone as a single therapy or in combination with another antibacterial agents. The fact that new strains of Acinetobacter baumannii started to show resistance to colistin obliged the investigators to search for other alternatives for treatment. The aim of this study was to assess the effect of combination of Doxycycline and co-trimethoxazole in the cure of nosocomial MDR-AB infection in critically ill patients and its effect on the patients outcome. The study was done on 50 adult critically ill patients who developed nosocomial isolated MDR-AB in the Critical Care Medicine Department of Alexandria University in Egypt and received combination of Doxycycline 100 mg twice daily With trimethoprime- sulphamethoxazole (co-trimethoxazole) in a dose of 80 mg Trimethoprime/400 mg Sulphamethoxazole twice daily for 1 week. patients who are allergic to the antibiotics used or those who did not continue 7 days treatment were excluded from the study. Approval of local ethical committee as well as consent from patients relatives were obtained. culture and sensitivity was repeated after 1 week treatment. The microbiological cure rate was 60 % as 30/50 patients were cured. The bestcure rate was in surgical site infection with 88.9 % (8/9) while the cure in pneumonia was56.7 % (17/30). Two cases with blood stream infection were not cured while (5/9) patients from those who had more than one site infection were cured. The total 30 days mortality was 20 % (10/50) while the mortality related infection was 12 %. We concluded that combination of Doxycycline and co-trimethoxazole can be used in the treatment of nosocomial MDR-AB infection resistant to colistin or incases with contraindications or unavailability of colistin especially in surgical site infection and to less extent in pneumonia. However, further larger studies are needed to validate the results of this study.