To compare the effectiveness of home versus hospital intravenous (IV) antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis (CF). A retrospective chart review was performed of 143 encounters for pulmonary exacerbations in 50 patients with CF. All encounters were categorized into two groups based on location of completion of antibiotic therapy: hospital group completed treatment in hospital (n = 64), home group completed treatment at home (n = 79). Percent change was calculated for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow rate between 25 percent and 75 percent of vital capacity (FEF25-75%), maximumforced expiratory flow (FEFmax), oxygen saturation (O2 SAT), and weight. Means of percent change (PC) from the beginning to the end of IV antibiotic treatment in outcome variables were compared. Total duration of treatment was compared between the two groups. The two groups had no significant differences at baseline in all outcome variables. Treatment of exacerbations in both groups resulted in significant improvement of lung function, O2 SATS, and weight (P≤ 0.001). The percent change in FEV1 was greater in hospital group versus home group (P=0.04). The duration of treatment was significantly shorter in the hospital group (P=0.001). Home and hospital IV antibiotic therapy resulted in significant improvement in lung function and weight. Hospital therapy, however, resulted in significantly greater improvement in FEV-1 and required less duration of treatment as compared to home treatment in children with CF.