Hospital-based comparative effectiveness (CE) centers provide a model that clinical leaders can use to improve evidence-based practice locally. The model is used by integrated health systems outside the US, but is less recognized in the US. Such centers can identify and adapt national evidence-based policies for the local setting, create local evidence-based policies in the absence of national policies, and implement evidence into practice through health information technology (HIT) and quality initiatives. Given the increasing availability of CE evidence and incentives to meaningfully use HIT, the relevance of this model to US practitioners is increasing. This is especially true in the context of healthcare reform, which will likely reduce reimbursements for care deemed unnecessary by published evidence or guidelines. There are challenges to operating hospital-based CE centers, but many of these challenges can be overcome using solutions developed by those currently leading such centers. In conclusion, these centers have the potential to improve the quality, safety and value of care locally, ultimately translating into higher quality and more cost-effective care nationally. To better understand this potential, the current activity and impact of hospital-based CE centers in the US should be rigorously examined.