Introduction Pseudomonas aeruginosa is the most commonly isolated organism in children with ventilator-associated tracheobronchitis (VAT). Enteral treatment with ciprofloxacin or levofloxacin is sometimes employed, but supportive data are limited. The purpose of this study was to evaluate the effectiveness and safety of enteral ciprofloxacin and levofloxacin administration for VAT in children. Methods This was a retrospective review of electronic medical records for children less than 18 years of age who received enteral ciprofloxacin or levofloxacin for the treatment of VAT from January 2013 through January 2020 at an academic children’s hospital. Results Seventy-six children (median age 9.5, IQR 3.6-13.1 years), received ciprofloxacin or levofloxacin for VAT treatment during the study period. Median treatment duration was 8 (range 7-10) days. Most tracheostomy cultures (n=70/82, 85%) were polymicrobial, with P. aeruginosa most commonly isolated (n=67/224 organisms, 30%). Sixty-five children (86%) were successfully treated with an enteral fluoroquinolone. Antibiotics were changed or extended for two (3%) children. Ten (13%) children were prescribed antibiotics and eight (11%) required hospitalization for a lower respiratory tract infection within 30 days of completion of their fluoroquinolone course. Six (8%) patients received a seizure rescue medication, seven (9%) experienced emesis, and one (1%) had elevated transaminases. Tendonitis, tendon rupture and QTc prolongation were not observed. Conclusions The results of this study suggest enteral fluoroquinolones may be effective for the treatment of VAT in children. Further study is warranted to clarify the role of these agents in pediatric VAT.