Since its inception in 2003, Medicare Part D has become the largest addition to the Medicare benefit since it was signed into law in 1965. Despite this novel prescription drug coverage, the design and benefit structure of Medicare Part D has been challenging for beneficiaries and healthcare providers alike. Beneficiaries have been faced with a plethora of drug plan offerings. Additionally, the unique benefit structure and annual variation in plan offerings and plan parameters have left beneficiaries unaware of gaps in coverage and reluctant to re-evaluate plan offerings. Despite these issues, to date the total out-of-pocket costs for beneficiaries enrolled in Medicare Part D have not been examined. To mitigate this void, three studies were conducted to determine trends in the total out-of-pocket costs incurred by Medicare beneficiaries enrolled in Medicare Part D prescription drug plans. Pharmacy claims data of 50 randomly sampled patients from a database of Medicare-eligible individuals were used to generate medication profiles. To maintain a patient-perspective approach, these profiles were then entered into the Plan Finder Tool on the Medicare website in order to determine the estimated annual costs for each stand-alone prescription drug plan in each Medicare region. It was determined that Medicare Part D plan costs increased from 2007 to 2008 in most regions, however in 13 of 34 regions patients may not have paid more if they were enrolled in the lowest cost plan each year. Based on these findings, the opportunity cost of neglecting to re-evaluate prescription drug plan offerings for 2008 was examined. A significant increase ranging from $277 to $562 was observed nationally if patients did not switch to the lowest cost plan. Only 12% of the plans remained the lowest cost plan in 2008. Lastly, prescription drug plan cost trends in California were examined from 2007 to 2009 and confirmed that the estimated annual cost of a plan was the most consistent plan parameter. Collectively these studies indicate that Medicare Part D beneficiaries must annually re-evaluate all prescription drug plan offerings in order to minimize out-of-pocket drug costs.