Background: The growing incidence of multidrug-resistant (MDR) bacterial infections has become a public health crisis. This work aims to evaluate the in-vitro activity of silver nanoparticles (AgNPs), alone and in combination with the antimicrobials amikacin and ceftazidime, against MDR Gram-negative bacilli (GNB) isolated from clinical cases in Zagazig University Hospitals. Methods: In a cross-sectional study, MDR GNB were isolated from different clinical specimens and were tested to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal activity of AgNPs using broth microdilution method. The effect of combining subMIC levels of AgNPs (MIC/2 and MIC/4) with amikacin and ceftazidime, was also determined by broth microdilution. Results: A total of 63 MDR GNB was obtained during the study period (22 E. coli, 17 Klebsiella, 15 Pseudomonas aeruginosa, and 9 Acinetobacter isolates). AgNPs demonstrated a bactericidal effect on all tested isolates with an MBC/MIC ratio of less than 4. When combined with amikacin, a synergistic effect was demonstrated on all tested E.coli and Klebsiella isolates at AgNPs MIC/2 and on 45.4%, 40%, and 77.8% of E.coli, P.aeruginosa and Acinetobacter isolates, respectively at MIC/4. In combination with ceftazidime, AgNPs exhibited a synergistic effect on 100% of E. coli and 88.2% Klebsiella at both MIC/2 and MIC/4 and on 40% of P. aeruginosa isolates at AgNPs MIC/4. Conclusions: AgNPs exert a bactericidal activity on MDR GNB as well as a synergistic effect when combined with amikacin and ceftazidime suggesting them as a new weapon in the war against MDR GNB.