Objective. To test clinical pathways in a variety of Italian health care organizations in 2000–2002 to measure performance in decreasing process and outcome variations. Design. Creation of indicators, specific for each clinical pathway, to measure variations in the care processes and outcomes. Pre- and post-analysis model to evaluate the possible effect of the clinical pathways on each indicator. Setting. We tested the clinical pathways in six sites, each with different clinical pathways. Results. Reductions in health care macro-variation phenomena (length of stay, patient pathways, etc.) and in performance micro-variation (variations in diagnostic and therapeutic prescriptions, protocol implementation, etc.) were shown in sites where pathways were implemented successfully. A significant improvement in outcome for patients who were treated according to the clinical pathway for heart failure was also demonstrated. Conclusions. The overall purpose of clinical pathways is to improve outcome by providing a mechanism to coordinate care and to reduce fragmentation, and ultimately cost. Our results demonstrated that it is possible to achieve this goal. Although controversial elements still exist, we think that clinical pathways can have a positive impact on quality in health care.