It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48-weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment.A post-hoc analysis of 2 identical randomised trials of ARD-3150 (ORBIT-3 and -4) administered 28-days on and 28 days off in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The quality of life bronchiectasis respiratory symptom scale (QOL-B-RSS), which has a 1-week recall period, was administered every 28-days. We examined whether respiratory symptoms improved during on-treatment periods and the relationship of changes in QOL-B-RSS to changes in bacterial load using a mixed model repeated measures approach.ARD-3150 treatment resulted in a significant improvement in respiratory symptoms during the on-treatment periods with concordant results between ORBIT-3 (estimate 1.4 points, standard error (se) 0.49, p=0.004) and ORBIT-4 (estimate 1.1 point, SE0.41, p=0.006). The proportion of patients achieving a symptom improvement above the minimum clinically important difference was higher with ARD-3150 compared to placebo during on-treatment cycles (p=0.024). Changes in respiratory symptoms were correlated with changes in bacterial load in the treatment group (r=-0.89, p<0.0001). Individual estimates for decrements in the QOL-B RSS during exacerbation were -9.4 points (se 0.91) in ORBIT-3 and -10.8 points (0.74) in ORBIT-4 (both p<0.0001).Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis.