The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.