Background: Patients with cystic fibrosis are at risk for impaired vitamin Ii status due to fat malabsorption from pancreatic insufficiency. This study was designed to assess vitamin Ii status and measure the effect of vitamin K-1 supplementation in cystic fibrosis patients. Methods: Eighteen outpatients participated in a crossover study to determine the effect of vitamin K-1 (phylloquinone) supplementation. After obtaining initial data, each subject was randomly assigned to either a 4-week study treatment of 5 mg oral vitamin K-1 supplementation per week, or no supplementation and then crossed over to the other treatment for a second 4 week period. Plasmal serum and urine samples were collected and analyzed pre-study and at the end of each study period. Results: The mean concentration of plasma vitamin K-1 for the supplemented group was significantly higher than the unsupplemented group, [0.34 nmol/L and 0.21 nmol/L, respectively (p < 0.05)]. The percent of undercarboxylated osteocalcin increased on supplementation from 17% to 31%, (p < 0.005). Prothrombin induced in vitamin Ii absence (PIVKA-II) increased on supplementation from 5 ng/mt to 22 ng/mL, (p < 0.005). The ratio of urinary gamma-carboxyglutamic acid/creatinine was similar for both study periods. Conclusions: In contrast to other studies in cystic fibrosis, this study demonstrated a need for vitamin K-1 supplementation. The carboxylation state of osteocalcin and PIVKA-II were the most sensitive indices of changes in vitamin K-1 status, Although the 5 mg vitamin K-1/week dose improved these vitamin Ii parameters, normal levels were not achieved.