Background: Intravenous tobramycin (three- times daily)is widely used for pu lmonary exacerbations in patients with cystic fibrosis who have chronic Pseudomo nas aeruginosa infection. We undertook a double- blind, randomized controlled t rial to assess the safety and efficacy of once versus three- times daily tobram ycin in these patients. Methods: 244 patients from 21 cystic- fibrosis centres in the UK were randomly assigned to once or three- times daily tobramycin (with ceftazidime) for 14 days. Treatment was given as 30- min infusions of tobramyc in in 0.9% saline. Primary outcome measure was change in forced expiratory vol ume in 1s (FEV1), over the 14 days of treatment, expressed as a percentage of th e predicted normal value for age, sex, and height. We also measured the change i n FEV1 expressed as a percentage of baseline. Secondary outcomes included change in serum creatinine. The study was powered for equivalence,and primary analysis was per protocol. Findings:219 patients (107 once daily, 112 three- times dail y) completed the study per protocol. None was lost to follow- up, although 20 d iscontinued intervention. Of 122 patients assigned to once daily treatment, thre e did not receive the study regimen. The mean change in FEV1 (% predicted) over 14 days was similar on the two regimens (10.4% [once daily] vs 10.0% [three - times daily]; adjusted mean difference 0.4% [95% CI - 3.3 to 4.1]). Mean % change in FEV1 from baseline was also similar in both treatments (21.9% v s 22.1% ; - 0.1% [- 8.0 to 7.9]). There was no significant difference in % change in creatinine from baseline (- 1.5% [once daily] vs 1.7% [three- times daily]). However, in children, once daily treatment was significantly less nephrotoxic than was thrice daily (mean % change in creatine - 4.5% [once daily] vs 3.7% [thrice daily]; adjusted mean difference - 8.0% , 95% CI - 15.7 to - 0.4). No patients developed hearing loss during the study, although two reported acute dizziness and were withdrawn from the study. Interpretation: Intravenous tobramycin has equal efficacy if given once or three- times daily ( with ceftazidime) for pulmonary exacerbations of cystic fibrosis. The once daily regimen might be less nephrotoxic in children. Background: Intravenous tobramycin (three-times daily) is widely used for pu lmonary exacerbations in patients with cystic fibrosis who have chronic Pseudomo nas aeruginosa infection. We undertook a double-blind, randomized controlled t rial to assess the safety and efficacy of once versus Methods: 244 patients from 21 cystic- fibrosis centers in the UK were randomly assigned to once or three-times daily tobramycin (with ceftazidime) for 14 days. Treatment was given as 30- min infusions of tobramyc in 0.9% saline. Primary outcome measure was change in forced expiratory vol ume in 1s (FEV1), over the 14 days of treatment, expressed as a percentage of th e predicted normal value for age, sex, and height. We also showed the change in FEV1 expressed as a percentage of baseline. Secondary outcomes included change in serum creatinine. The study was powered for equivalence, and primary analysis was per protocol. Findings: 219 patients (1 07 once daily, 112 three-times dail y) completed the study per protocol. None was lost to follow-up, although 20 d is continuous therapy. Of 122 patients assigned to once daily treatment, thre e did not receive the study regimen. The mean change in FEV1 (% predicted) over 14 days was similar to the two regimens (10.4% [once daily] vs 10.0% [three times times]; adjusted mean difference 0.4% [95% CI - 3.3 to 4.1]). Mean% change in FEV1 from baseline was also similar in both treatments (21.9% vs 22.1%; -0.1% [-8.0 to 7.9]). There was no significant difference in% change in creatinine from baseline (- 1.5% [once daily However, in children, once daily treatment was significantly less nephrotoxic than was thrice daily (mean% change in creatine - 4.5% [once daily] vs 3.7% [thrice daily]; adjusted mean difference - 8.0%, 95% CI - 15.7 to - 0.4). No patients developed hearing loss during the study, although two reported acute dizziness and were withdrawn from the study. Interpretation: Intravenous tobramycin has equal efficacy if given once or three-times daily (with ceftazidime) for pulmonary exacerbations of cystic fibrosis. The once daily regimen might be less nephrotoxic in children.