AIM: To determine the effect of long-term tobramycin (TOB) inhalation therapy on recurrent pneumonia among ventilator-dependent children with profound neurological disabilities. METHODS: TOB inhalation was performed in eight series of trials in seven ventilator-dependent children who had intratracheal Pseudomonas aeruginosa and suffered from recurrent pneumonia. Their age at the initiation of therapy was 68 ± 50 months (mean ± standard deviation), whereas the duration of treatment was 30 ± 22 months. The participants were followed after the termination of therapy for a period of 38 ± 32 months. RESULTS: The annual rate of pneumonia was 5.6 episodes per year (n = 8) preceding the initiation of inhalation, which decreased to 3.7 (n = 8), 1.6 (n = 5), and 0.67 (n = 3) in the periods of 0-12, 12-24, and 24-36 months after initiation, respectively. The rates were 1.0 (n = 6), 0.6 (n = 5), and 1.4 (n = 5) in the periods of 0-12, 12-24, and 24-36 months after the termination of therapy. INTERPRETATION: Extended TOB inhalation therapy was effective in decreasing the morbidity of pneumonia in ventilator-dependent children with severe motor and intellectual disabilities.