Implementation of patient safety initiatives can be costly in time and energy. Because of small volumes and limited resources, rural hospitals often are not included in nationally driven patient safety initiatives. This article describes the Tennessee Rural Hospital Patient Safety Demonstration project, whose goal was to strengthen capacity for patient safety initiatives in 8 small Tennessee rural hospitals using a multi-organizational collaborative model. The demonstration identified and facilitated implementation of 3 patient safety interventions: the Agency for Healthcare Research and Quality (AHRQ) patient safety culture survey, use of personal digital assistants (PDAs), and sharing of emergency room protocols. The experience suggested that a collaborative model between rural hospitals, a payer, a hospital association, a quality improvement organization, and academic institutions can effectively support patient safety activities in rural hospitals. Successful implementation of the 3 patient safety interventions depended on leadership provided by nursing and patient safety/quality managers and open, trusting communications within the hospitals.