Comparative Effectiveness Research (CER) has become positioned to inform health care decision-making with passage of the health care reform law, "Patient Protection and Affordability Care Act of 2010". As the name suggests, CER attempts to understand the relative efficacy between two therapies to allow clinicians, health care providers, and others to make rational decisions when evaluating therapeutic options. This is particularly relevant in the nephrology community as the dawn of bundled payments approaches. The current evidence base for CER studies is especially curtailed as a result of limited head-to-head clinical trials in patients with end-stage renal disease. Specifically, CER for available oral vitamin D agents approved for use in ESRD is lacking. The inclusion of oral vitamin D in the bundled payment system in 2011 may lead more clinicians to examine which oral vitamin D analog to prescribe to their patients, making this an especially timely topic.