Central venous catheter (CVC)-associated infections have substantial impacts on morbidity, mortality, and overall cost of health care. Acinetobacter baumannii causes severe infections, survives on abiotic surfaces, colonizes and develops resistant biofilm on different medical devices including CVC. The cranberry contains proanthocyanidines which possess antiadherent activity against colonic bacteria. This study aimed to assess the use of moxifloxacin/cranberry extract combination against A. baumannii biofilm established on CVC. A. baumannii bioflim was developed on silicone CVC and visualized by electron microscopy. The biofilm was treated according to the method described by Aslam et al. Briefly, segments (1 cm) of silicone CVC (Cook, Inc., Bloomington, IN) were incubated in bacterial suspensions (106 CFU/ml) in Mueller Hinton broth to allow biofilm formation. After incubation at for 24 h, segments were aseptically removed. Four sets of catheter segments (3 segments/each) were suspended for 6 h at in one of the following solutions: moxifloxacin (0.16 ug/mL), cranberry aqueous extract (10 mg/mL), Mox-Cran combination, or normal saline (NS) as a control. Catheter segments were rinsed 3 times with NS to remove planktonic bacteria. These segments were individually sonicated for 5 min and vortexed for 30s in 1 ml NS. Aliquots (100 uL) of the sonicated fluids and their dilutions were inoculated onto Mueller Hinton agar plates. Each set of experiments was repeated three times. Bacterial colonies (CFU/cm) were counted after incubation for 24 h. The average colony count of each set of experiment was calculated. The average values of the treated sets were divided by the average value of the control percent for calculation of the percentage biofilm reduction in each treatment as compared to the untreated control (NS). Using ANOVA, the significance level for all analyses was . The effect of moxifloxacin alone was similar to the untreated control. Cranberry extract could reduce the biofilm by almost 90%. Moreover, MoxDran combination could synergistically and completely (100%) eradicate. A. Baumannii biofilm from CVC. There is a dire need for developing novel strategies against microbial biofilms on medical devices, such as the use of combination between safe anti-adherent extracts with antimicrobial agent as a catheter lock solution, to retrieve the infected vascular catheters. The results of this study revealed a promising antibiofilm activity of moxifloxacin/cranberry extract combination for eradication of mature A. baumannii biofilm from CVC (therapeutic approach). Since biofilm prevention is much easier than its eradication, we hypothesize that impregnation or coating of medical devices, including CVC, with such novel and safe combination might be an outstanding tool against biofilm development (prophylactic approach).