Introduction: Acinetobacter baumannii is a multidrug-resistant bacterium commonly associated with hospital-acquired infections. The rapid spread of A. baumannii has raised concerns, as it has been linked to the emergence of clones in healthcare facilities worldwide. The challenges of treating and controlling infections caused by this bacterium in hospital settings are exacerbated by its resistance profile. The proliferation of clones worldwide highlights the need for careful infection control procedures and new tactics to fight illnesses caused by drug-resistant A. baumannii strains. Materials and Methods: Between January 2019 and December 2020, a total of 26,250 specimens were collected by personnel from the Department of Microbiology at King Fahad Specialist Hospital. Results: Our study highlights a significant surge in antimicrobial resistance, indicating a relative increase in multidrug-resistant A. baumannii isolates. Despite extensive resistance, azithromycin, cefoxitin, norfloxacin, penicillin, piperacillin, tetracycline, ceftriaxone, nitrofurantoin and aztreonam showed 91.2%–100% efficacy against these strains. Conclusions: This study emphasises the critical need for stringent infection control measures and judicious antibiotic strategies to curb multidrug-resistant A. baumannii outbreaks in healthcare settings. The identification of alternative therapies is imperative for improved management of infections caused by multidrug-resistant A. baumannii.