OBJECTIVE:We assessed incidence of liver cirrhosis, risk factors for developing cirrhosis, and if there is an association between hormonal contraception (HC) use and liver cirrhosis among reproductive-aged females with cystic fibrosis (CF). STUDY DESIGN:Between January 2021 and April 2022, we recruited reproductive-aged females with CF to complete a questionnaire. We linked their responses to the Cystic Fibrosis Foundation Patient Registry (CFFPR) to examine potential risk factors for incident liver cirrhosis and its association with time-varying HC using survival analysis. RESULTS:Among 551 persons with CFFPR survey and registry data, 8 had cirrhosis at first available registry report and 3 were excluded for other reasons. Of the 540 remaining participants, 250 (46.3%) were F508 homozygous, 437 (80.9%) were using modulators, and 28 (5.2%) had new onset cirrhosis. Genotype and modulator use were not associated with cirrhosis incidence (adjusted hazard ratios (aHR) 0.57 with 95% confidence interval (CI) 0.15-2.22 and 0.86 with CI 0.24-3.11, respectively). Over all 5146 years of reporting including a median of 12 years per person, 64.9% of years involved reported non-HC, 23.6% combined HC, and 11.5% progestin-only HC. HC use was not associated with cirrhosis incidence (aHR 0.68 with CI 0.25-1.86 for combined HC and 0.57 with CI 0.13-2.49 for progestin-only HC). CONCLUSION:In our observational cohort, the incidence of cirrhosis was 5.2%. HC use is not associated with liver cirrhosis. Future research should explore the risk factors in CF for developing liver cirrhosis and its relation with HC use. IMPLICATIONS:In females with cystic fibrosis, hormonal contraception is not associated with liver cirrhosis.