Background: Vitamin D deficiency is common in CKD and dialysis patients. Studies suggest a physiologic autocrine and/or paracrine role for 1,25(OH)D produced via 1α-hydroxylase in tissues such as vascular smooth muscle, breast, prostate, and bone marrow. Studies have not yet defined the optimal dose and duration of vitamin D necessary to replete and maintain stores in dialysis patients, or whether it is safe or beneficial. Methods: We performed a review of the prevalence of vitamin D deficiency and the safety and effectiveness of ergocalciferol oral supplementation (vitamin D<sub>2</sub>, 50,000 IU monthly) given to hemodialysis patients during dialysis May to October 2005 in St. Louis (latitude 38°). Results: Among the 119-patient cohort present for the entire 6 months, 25(OH)D was (mean ± SD) 16.9 ± 8.5 ng/ml, (91% < 30 ng/ml) and increased to 53.6 ± 16.3 ng/ml (p < 0.001), (95% > 30 ng/ml, and none > 100 ng/ml). Initial versus 6 mo. serum calcium (9.1 ± 0.56 vs. 9.2 ± 0.70), phosphorus (5.25 ± 1.38 vs. 5.11 ± 1.31), Ca × P, and paricalcitol dose (10.3 ± 9.6 vs. 11.3 ± 9.2 mcg/week) were not significantly different. No hypercalcemia could be attributed to supplementation. Mean hemoglobin did not change significantly (11.96 ± 1.4 vs. 11.69 ± 1.4, p = 0.124), but most patients experienced a reduced weekly epoetin dose. Epoetin dose decreased in 64% of patients, and increased in 28%. Conclusions: We conclude that the vast majority of hemodialysis patients are vitamin D-deficient; monthly ergocalciferol 50,000 IU is safe and effective in normalizing serum 25(OH)D levels and may have an epoetin-sparing effect.