Background: Comparative effectiveness research (CER) has come to remain at the forefront of political and scientific debates of health care. The aim of this article is to describe the attributes of CER and implications to the field of urology. Methods: The authors reviewed the published urology literature and recent CER publications including the Institute of Medicine reports. Results: CER is defined as the evaluation of the relative efficacy of diagnostic tests, treatments, and health care services against the current standards of care, with the goal of reducing health care costs while simultaneously improving quality. Significant government funds were recently devoted to CER efforts. The Institute of Medicine identified 25 of the most urgently needed areas for research of which three pertain to Urology: screening for prostate cancer, comparing effectiveness of treatments for localized prostate cancer, and use of imaging in diagnosing, staging, and monitoring cancer patients. Some of the important required strategies to formulate successful CER include involving health care stakeholders to aid in selecting appropriate topics, utilizing study populations that represent real life practice, and the development of large-scale national databases and registries. Conclusion: Several topics of urologic care have already been identified in the first quartile of CER priorities, and many others need to be added. Following the proposed research, designs for CER should be done while abiding by robust methodology, maintaining transparency, and effectively translating research into clinical practice. © 2010 Springer-Verlag.