To assess the effectiveness of an intervention designed to increase compliance with national asthma care guidelines in primary care safety net health centers serving high-disparity patient populations, we conducted a group-randomized controlled trial (seven intervention sites and nine control sites) in federally funded community health centers in eight southeastern states. There were three components involved in the intervention: resources (asthma kits including peak flow meter, MDI spacer device, plus educational materials), training of all health center staff in asthma care guidelines, and tools or templates for practice-level systems change (asthma flow sheets and standing orders). Control group sites received only copies of the national asthma guidelines. Chart reviews were performed to determine practitioner's compliance with national guidelines for asthma care. Clinicians practicing in intervention health centers showed significantly (p < 0.01) greater improvement on some measures than did the control health centers, although postintervention compliance with guidelines was still suboptimal. Disseminating national guidelines is not enough. Providing training and guideline-specific resources, in combination with tools for practice change, improved care significantly even in safety net health centers serving high-disparity patient populations.