Pain management guidelines advise opioids for the management of chronic moderate to severe pain, both malignant and non-malignant. Among the options for opioid therapy, oral opioids and transdermal fentanyl offer patient convenience and cost advantages over parenteral (e.g., IV or IT) administration. After efficacy, patient convenience and cost are primary criteria in selecting chronic pain control therapy. In order to better understand the distinctions in these criteria, an economic framework for evaluating transdermal fentanyl and oral opioids is needed. OBJECTIVE: To develop an economic framework for evaluating transdermal fentanyl and oral opioids for management of chronic moderate to severe malignant and non-malignant pain. METHODS: Based on a systematic review of the literature, a decision analytic model was developed. It is comprised of three phases--Titration (lasting up to several days), Stabilization (30 days), and Long-Term Use (through the first year). The primary outcomes are costs, quality-adjusted life-days (QALDs), and incremental cost-utility ratios. Probabilities of events and disutility values were determined from clinical trials of transdermal fentanyl, controlled release morphine, and controlled release oxycodone, supplemented when necessary with expert opinion. Costs were derived from publicly available data. RESULTS: The key cost drivers are opioid price, the probability of switching to an alternative therapy, and the cost of treating nausea and vomiting. The primary parameters influencing QALDs are the probability of sustained pain control and the probability and disutility of chronic constipation. CONCLUSION: This model may be used to guide data collection in head-to-head clinical trials, and may be used by individual decisionmakers to inform selection of the optimal opioid for chronic pain management.