Background The prevalence of Achromobacter spp. in cystic fibrosis (CF) has increased while its significance remains controversial. Our aim was to investigate the impact of Achromobacter spp. isolation on clinical outcomes in children with CF. Methods Children with Achromobacter spp. isolation were retrospectively included from the CF database of our center. Control groups of children with CF, who had never been infected by Achromobacter spp., were individually case-matched by age, sex, and Pseudomonas aeruginosa isolation status. Pulmonary function and exacerbation frequency were compared between groups during follow-up. Results Thirty-seven children had at least one respiratory specimen positive for Achromobacter spp. Achromobacter spp. were chronically isolated from 15 (40.5%) and intermittently from 22 (59.5%) of these 37 children. Although the baseline forced expiratory volume in 1 s (FEV1) z-score was similar between the Achromobacter spp.-infected and -uninfected groups (-0.65 +/- 2.22 vs. -0.15 +/- 1.30, respectively; p = 0.318), children infected by Achromobacter spp. had a lower FEV1 z-score compared to the control group by the end of the first year (-1.37 +/- 2.17 vs. -0.14 +/- 1.65, respectively; p = 0.025). In addition, the FEV1 decline in 1 year was significantly greater in the group infected by Achromobacter spp. compared to the uninfected group (-1.18%/year vs. -9.07%/year, respectively; p = 0.043). Furthermore, the cumulative numbers of exacerbations observed in the Achromobacter spp.-infected group were higher compared to the control group by the end of the second year (4 [0-17] versus 3 [0-9], respectively; p = 0.001). Conclusions Achromobacter spp. isolation is associated with more accelerated decline in lung function parameters and frequent exacerbations in children with CF.