Severe liver disease affects 4.5% to 10% of individuals with cystic fibrosis (CF) and is the third-leading cause of death. Liver transplantation (LT) is an accepted therapy, but the effects of liver disease and LT on pulmonary function in patients with CF are controversial. Our aim was to characterize changes in pulmonary function in LT patients with CF. Using mixed effect models, we analyzed pulmonary function before and after transplantation in 168 LT patients and 840 non-LT patients with CF who were matched by age, sex, pancreatic status, infections with US CF Foundation Patient Registry data (1989-2007). The primary outcome was the change in the forced expiratory volume in 1 second (FEV1; percent predicted) in LT and non-LT in the 3-years periods before or after transplantation; second we compared FEV1 changes. In the 3 years before transplantation, LT had lower initial FEV1 values (71.5% ± 1.9%, P < 0.001) and a slower decline (+0.1% ± 0.4%/year, P < 0.001) than non-LT (79.6% ± 1.3% and −1.3% ± 0.2%/year, respectively). There was no difference in the FEV1 decline after transplantation (−1.4% ± 0.4%/year for LT versus −2.1% ± 0.2%/year for non-LT, P = 0.14). Both the (P = 0.003) and (P = 0.001) had a slower FEV1 decline in the period before transplantation versus after transplantation. In conclusion, pulmonary function is lower and declines more slowly in patients with CF before LT versus, but parallels the decline in non-LT after transplantation. LT is neither beneficial nor detrimental to pulmonary function in CF but returns FEV1 decline to the same trajectory found for matched non-LT individuals with CF. Liver Transpl, 2012. © 2012 AASLD.