Background The ACHIEVE (Optimizing the Treatment of Secondary Hyperparathyroidism: A Comparison of Sensipar and Low Dose Vitamin D vs Escalating Doses of Vitamin D Alone) trial evaluated the efficacy of treatment with cinacalcet plus low-dose activated vitamin D analogues (Cinacalcet-D) compared with vitamin D analogues alone (Flex-D) in attaining KDOQI (Kidney Disease Outcomes Quality Initiative) targets for secondary hyperparathyroidism (SHPT). The economic implications of these treatment regimens have not been explored. Study Design: Economic analysis of SHPT treatment in hemodialysis patients. Setting & Population: This analysis used data from the ACHIEVE trial, in which patients received either Cinacalcet-D or Flex-D. Model, Perspective, & Time Frame: We assessed the relative cost-effectiveness of these regimens in treating SHPT during the 27-week ACHIEVE trial, using a US payer perspective, with medication costs valued in 2006 US dollars. Intervention & Outcomes: Relative cost-effectiveness was assessed using cost-minimization analysis or incremental cost-effectiveness ratios. Effectiveness was measured using biochemical markers. Results: Mean medication costs per patient were $5,852 and $4,332 for the Cinacalcet-D and Flex-D treatment arms, respectively. There were no significant differences for the primary end point (parathyroid hormone level of 150-300 pg/mL and calcium-phosphorus product <55 mg2/dL2) and several of the secondary end points, rendering Cinacalcet-D more costly than Flex-D. For secondary end points, for which Cinacalcet-D was more effective, incremental cost-effectiveness ratios ranged from $2,957 (calcium <9.5 mg/dL) to $22,028 (all KDOQI targets) per patient reaching target. Switching to generic calcitriol would have increased the cost difference between treatment arms ($2,079), whereas switching sevelamer to lanthanum decreased the difference ($1,426). Limitations: Costs and outcomes were derived from a short-term randomized controlled trial and were protocol driven. Clinical outcomes, such as mortality, were not available. Long-term economic conclusions cannot be drawn from these data. Conclusions: Cinacalcet combined with vitamin D analogues was no more effective than vitamin D analogues in achieving the primary ACHIEVE end point and incurred greater costs. This conclusion was not tempered substantially by the cost of vitamin D analogues or oral phosphate binders. Whether the additional costs of cinacalcet are warranted will require longer term models to determine whether changes in serum levels of mineral metabolic markers translate into lower morbidity, mortality, and downstream costs. © 2010 National Kidney Foundation, Inc.