Pneumonia is a major cause of morbidity and mortality in the United States. Therefore, prevention of pneumococcal pneumonia by administering effective and well-tolerated vaccines is an important goal, especially in the immunocompromised patients who are at an increased risk of infections. At a large Midwestern Veterans Affairs Rheumatology Clinic, an internal audit revealed a baseline immunization rate of 3%. Through the Lean Six Sigma approach, the investigators sought to increase the rate to 70%. An interprofessional approach incorporating provider education, reinforcement at the point of care, and workflow simplification was sequentially implemented. Lean Six Sigma tools, including process mapping, voice of the customer, and statistical process control charts were utilized. These interventions increased the percentage of eligible patients receiving vaccinations from 3% (n = 19/687) to 23% (n = 11/48) and decreased the vaccine administration time from 15 to 7 minutes. No adverse reactions were reported. This was balanced by an increase in appointment time by 4 minutes in those who received vaccines. The Lean Six Sigma approach was critical to reducing waste and improving value for patients and providers by increasing pneumococcal vaccination rates among the immunocompromised veteran population in a Midwestern Veterans Affairs Rheumatology Clinic.