<i>Background:</i> Renal osteodystrophy is one of the major complications in patients with chronic renal failure. Large C-PTH fragments are secreted from the parathyroid glands and exert antagonistic actions against PTH-(1–84). The PTH-(1–84)/large C-PTH fragments ratio reflects both biosynthesis and processing of PTH; however the alteration of the ratio under vitamin D therapy has not been investigated. <i>Methods:</i> Seventeen hemodialysis patients with intact PTH levels of >300 pg/ml were enrolled. Calcitriol or maxacalcitol were administered intravenously for 78 weeks. Intact PTH, PTH-(1–84), and the PTH-(1–84)/large C-PTH fragments ratio were measured at 0, 13, 26, 52 and 78 weeks. <i>Results:</i> Intact PTH and PTH-(1–84) levels, which were 492.0 ± 115.7 and 303.4 ± 105.4 pg/ml, respectively, at baseline, significantly decreased at the end of the study to 268.9 ± 121.9 (p < 0.0001) and 190.7 ± 106.9 pg/ml (p = 0.0008), respectively. In contrast, large C-PTH fragments, which were 152.7 ± 53.5 pg/ml at baseline, did not significantly change at 78 weeks (144.5 ± 72.2 pg/ml, p = 0.7612). Consequently, the PTH-(1–84)/large C-PTH fragments ratio was significantly reduced from 2.25 ± 1.31 to 1.47 ± 0.89 (p = 0.0004). <i>Conclusion:</i> The PTH-(1–84)/large C-PTH fragments ratio reflects the change of PTH biosynthesis, processing and secretion from the parathyroid glands, and it may be a beneficial marker to evaluate the overall biological PTH action and predict bone turnover status in hemodialysis patients under intravenous vitamin D therapy.