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Objectives To test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars Practice Transformation Program, to increase adult pneumococcal vaccination. Design Randomized controlled cluster trial ( RCCT) in Year 1 (June 1, 2013 to May 31, 2014) and pre-post study in Year 2 (June 1, 2014 to January 31, 2015) with data analyzed in 2016. Baseline year was June 1, 2012, to May 31, 2013. Demographic and vaccination data were derived from deidentified electronic medical record extractions. Setting Primary care practices (n = 25) stratified according to metropolitan area (Houston, Pittsburgh), location (rural, urban, suburban), and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n = 13) or Year 2 (n = 12). Participants Individuals aged 65 and older at baseline (N = 18,107; mean age 74.2; 60.7% female, 16.5% non-white, 15.7% Hispanic). Intervention The 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine ( PPSV) and pneumococcal conjugate vaccine ( PCV) vaccination rates and percentage point ( PP) changes in vaccination rates. Results In the Year 1 RCCT, PPSV vaccination rates increased significantly in all intervention and control groups, with average increases ranging from 6.5 to 8.7 PP (P < .001). The intervention was not related to greater likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh but not in Houston. Conclusion In a RCCT, PPSV vaccination rates increased in the intervention and control groups in Year 1. In a pre-post study, private primary care practices actively participating in the 4 Pillars Practice Transformation Program improved PPSV and PCV uptake significantly more than practices that were in the maintenance phase of the study. [ABSTRACT FROM AUTHOR]