Background: The optimal treatment for correcting or preventing vitamin D insufficiency in cystic fibrosis (CF) patients has not been established. Objective: The aim of the study was to assess the relative efficacy of three modes of vitamin D therapy: cholecalciferol (D3), ergocalciferol (D2), and UV light in raising or maintaining 25(OH)D levels above 30 ng/ml. Design: Thirty adult CF subjects with vitamin D insufficiency were randomized into one of three treatment arms: D3, D2, or UV light. Subjects randomized to D3 or D2 ingested 50,000 IU of vitamin D weekly, and those randomized to UV exposed their skin to UV light from a lamp five times a week. Serum was collected for 25(OH)D and PTH at baseline and at 12 wk. Results: Treatment with D3 and D2 raised 25(OH)D levels significantly, from a mean of 21.2 ± 10.18 to 47.1 ± 20.5 ng/ml (P < 0.001) and 24.4 ± 10.3 to 32.7 ± 9.7 ng/ml (P = 0.01), with 100% and 60% reaching 25(OH)D levels above 30 ng/ml, respectively. Treatment with UV did not raise 25(OH)D levels significantly; however, only 55% of subjects were adherent with UV therapy. Conclusion: This study demonstrates that CF subjects are able to achieve or maintain optimal vitamin D status (>30 ng/ml) with two oral regimens of either D3 or D2 treatment, the former being more efficacious. A confounding variable for this observation is the fact that the D3 and D 2 capsules contained different carriers, powder-based vs. oil-based, respectively. UV therapy did not alter vitamin D status, possibly due to poor adherence to UV therapy. Copyright © 2009 by The Endocrine Society.