During the recent years, cinacalcet has markedly improved the management of hyperparathyroidism in patients on hemodialysis. However, to the best of our knowledge, there are no specific studies addressing the dose regimen of cinacalcet. The aim of the study was to evaluate the efficacy of cinacalcet on the achievement of targets in the treatment of hyperparathyroidism in two different dosage schedules. Twenty-seven adult patients who were on hemodialysis for more than four months and with severe secondary hyperparathyroidism (intact parathyroid hormone (iPTH) >88 pmol/L) resistant to conventional treatment were included in this prospective study. We used the targets of K/DOQI-clinical guidelines as optimal target of iPTH, calcium and phosphate. Group 1 received a single daily administration of 30 mg of cinacalcet along with the main meal as the starting dose, and the dose was titrated thereafter monthly. Group 2 received cinacalcet with the main meal twice weekly starting with a dose of 90 mg on the first day of the week and 120 mg at midweek and titrated thereafter monthly. The levels of iPTH decreased significantly (P = 0.0001) from 124.00 ± 44.77 pmol/L to 37.78 ± 12.49 pmol/L and from 109.61 ± 53.13 pmol/L to 33.93 ± 12.03 pmol/L after 12 weeks in groups 1 and 2, respectively. After 12 weeks, alkaline phosphatase declined significantly (P = 0.0001) from 143.42 ± 75.20 IU/L to 87.42 ± 14.46 IU/L in group 1 (P = 0.013), and from 148.00 ± 108.49 IU/L to 101.61 ± 46.62 IU/L in group 2 (P = 0.05). There were no significant differences between the reductions of iPTH, calcium phosphate product and alkaline phosphatase levels in both the groups in the vertical comparison at the end of the study. There was no noteworthy difference in side effects between both the groups. Our results indicate that cinacalcet twice weekly is reasonably safe and effective in suppressing high PTH levels in hemodialysis patients, with fewer side effects.