Background: Vitamin D deficiency is highly prevalent and associated with secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend treatment of vitamin D deficiency starting with CKD stage 3, though no data are available showing an impact on serum parathyroid hormone (PTH) concentrations. The goal of this analysis, therefore, was to determine the effect of ergocalciferol treatment on plasma PTH concentrations in vitamin D-deficient patients with stage 3 and stage 4 CKD. Methods: A prospective, nonrandomized observational analysis was conducted in an academic community hospital CKD clinic. Fifty-two patients with stage 3 or stage 4 CKD with vitamin D deficiency and elevated PTH concentrations received ergocalciferol dosed per a modified K/DOQI guidelines protocol and adjusted every 3 months. Serum PTH, 25-vitamin D, 1,25-vitamin D, calcium, phosphorus, and albumin levels were drawn at initiation of therapy and repeated every 3 months. Results: The mean 25-vitamin D levels normalized in patients with stage 3 and 4 CKD, with values of 31.6 ± 2.2 ng/ml (78.8 ± 5.49 nmol/l) and 35.4 ± 1.9 ng/ml (88.4 ± 4.74 nmol/l), respectively (p < 0.0001). A median decrease in PTH concentrations of 13.1 and 2.0% was noted in patients with stage 3 and stage 4 CKD, respectively (p = 0.041, p = nonsignificant). Conclusions: Ergocalciferol therapy is a reasonable initial therapy for vitamin D deficiency associated with elevated PTH levels in stage 3 CKD. It does not appear to have equivalent benefits in stage 4 CKD.