Background Vitamin D insufficiency and deficiency are very common in patients with chronic kidney disease (CKD). The effect of ergocalciferol administration on serum 25-hydroxyvitamin D and plasma intact parathyroid hormone (PTH) levels in these patients is not known. Study Design Retrospective study. Setting & Participants Patients with CKD stage 3 or 4 who had a serum 25-hydroxyvitamin D level less than 30 ng/mL (<75 nmol/L) and increased plasma intact PTH level were treated with 50,000 IU of ergocalciferol once weekly for 12 weeks and once monthly thereafter for a total of 6 months. Patients were excluded if they had a history of active vitamin D sterol use. Outcome & Measurements 25-Hydroxyvitamin D and intact PTH were measured at baseline and follow-up. Results 66 patients met inclusion criteria. Average age was 70.4 ± 1.3 (SE) years (range, 40 to 88 years), and 97% were men. There were 44 patients (66%) with CKD stage 3 and 22 patients (33%) with CKD stage 4. After a median follow-up of 6 months, there was a significant increase in 25-hydroxyvitamin D levels from 16.6 ± 0.7 to 27.2 ± 1.8 ng/mL (41 ± 2 to 68 ± 4 nmol/L; P < 0.05) and a significant decrease in plasma intact PTH levels from 231 ± 26 to 192 ± 25 pg/mL (ng/L; P < 0.05). A multivariate logistic regression model showed that an increase in 25-hydroxyvitamin D level greater than 5 ng/mL (>12 nmol/L) is associated with a significant likelihood of a greater than 30% decrease in plasma intact PTH level (odds ratio, 4.5; 95% confidence interval, 1.5 to 15.1; P < 0.05). Although posttreatment 25-hydroxyvitamin D levels were not different between patients with CKD stages 3 and 4, only patients with CKD stage 3 had a significant decrease in plasma intact PTH levels. Limitations This is a retrospective study with mostly male patients. Conclusions Results show that ergocalciferol administration has a favorable effect on PTH levels if therapy results in an increase in 25-hydroxyvitamin D levels; this effect is more evident in patients with CKD stage 3.