Background This retrospective audit was undertaken to compare the efficacy of home intravenous (IV) antibiotic therapy, hospital IV antibiotic therapy and a combination of these 2 approaches, as determined by spirometric measures of lung function in cystic fibrosis (CF) patients, each with an acute respiratory exacerbation. Methods Pulmonary function, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow rate between 25 per cent and 75 per cent of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were compared between groups at the beginning and at the end of an IV antibiotic course. Results Treatment of exacerbations resulted in a significant improvement (p<0.05) in lung function irrespective of where patients were treated. The percentage improvement in FEV1 FVC, and FEF25-75 were significantly greater in patients treated in hospital compared to those who had home IV treatment (p<0.05). Conclusion Hospital IV antibiotic therapy resulted in greater improvements in FEV1 FVC and FEF25-75 than home IV antibiotic therapy in CF patients with an acute respiratory infection.