ISSUE: Hand hygiene (HH) has been demonstrated to be effective in preventing spread of infection in healthcare settings. Despite the evidence, compliance is reported to be suboptimal. The Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Healthcare Settings identified a number of factors adversely affecting HH compliance. Our health system worked in partnership with another to initiate a "six sigma" HH improvement project. The DMAIC (define, measure, analyze, improve, control) process was used to evaluate HH in a 20-bed medical surgical intensive care unit and create an improvement plan to increase and sustain compliance with HH practices among healthcare workers. PROJECT: Trained observers were used to conduct observations to establish baseline compliance. A survey was carried out to establish baseline knowledge and satisfaction regarding HH practices and supports. A stakeholders' analysis was done to identify key personnel who would influence project outcomes. A process map was developed to outline each step in the HH process and a cause-and-effect matrix was developed to prioritize key process inputs. Critical influencing factors were analyzed using a failure modes and effects analysis to identify process failures and causes to address in the improvement plan. Using multivariate studies and in consideration of the survey, improvement opportunities were identified for the action plan. The plan focused on five influencing factors: training/awareness, decision-making, hand hygiene opportunities, supply convenience/availability, and empowerment to remind. Tactics to address each factor were identified and implemented. After the improvement phase, key metrics and tactics were placed into a control plan. RESULTS: Baseline HH compliance was reported at 36%, with a range of 9% to 77%, depending on the type of HH opportunity observed. Compliance after the improve tactics were implemented rose to 65% (p=<0.001), with a range of 27% to 100%, dependent upon the type of hand hygiene opportunity. Use of the waterless alcohol-based sanitizer at baseline was 21 units/1000 patient days. Usage increased to 42 units/1000 patient days after the improve phase. LESSONS LEARNED: The six sigma approach ties improvement methods directly together with identified process failures. This analysis results in enhanced identification of specific improvement opportunities and also supports development of a control plan to be used to sustain gains in compliance.