OBJECTIVES: To develop an expected-cost model to examine the impact of opioid rotation among patients with chronic non-cancer pain from the payor perspective METHODS: A decision tree was developed depicting pathways a patient may follow over the course of 1 year while taking long acting opioids. Up to 2 switches and 5 dose adjustments were possible for each of the three treatment arms: 1) MS Contin ER switch to OPANA ER; 2) MS Contin ER switch to OxyContin ER; and 3)OPANA ER switch to OxyContin ER for patients where morphine is not an appropriate first line treatment option. Cost data included drug acquisition costs for extended release (ER) and immediate release (IR) opioids, physician contact reimbursement for pain specialists and primary care physicians. Estimated rates for side effects were assumed similar for the most frequently reported side effects (constipation, nausea, somnolence and sedation) and were applied to all treatment arms. RESULTS: A total of 149 possible pathways of care were evaluated among the 3 treatment arms. Assuming a BID regimen, expected-cost range for treatments 1, 2, and 3 were: $3426 – $4299, $3829 - $5073, and $4556-$5098, respectively. IR cost contribution of the total expected-cost for treatment arms 1, 2, and 3 amounted to 17%, 21% and 24%, respectively, and was dependent on the total daily ER dose. CONCLUSION: Opioid rotation is thought to be the result of the need to switch opioids when a therapy is not well tolerated by the patient. Having an effective alternative for rotation/switching if first line treatment fails has the potential to reduce incremental down stream costs by decreasing physician contacts due to dose adjustment or the need for further switching. Furthermore, the lack of effective pain management combined with non-tolerated side effects may also require the need for additional medications for pain (IR) and side effects.