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Background: Hand hygiene (HH) is central in prevention of health care-associated infections. In low resource settings, models to improve HH compliance are needed. We implemented a continuous quality improvement (CQI) program targeting HH in two hospitals in Kenya. Objective: To determine the impact of the HH CQI program and identify factors associated with HH compliance between 2018 and 2019. Methods: A CQI project targeting the improvement of hand hygiene was implemented, including training and mentorship. Data were collected monthly between April 2018 and December 2019 in Thika and Kitale Hospitals. Healthcare workers trained on Infection Prevention and Control (IPC) observed and recorded HH opportunities and subsequent compliance among staff, including nurses, clinicians, and auxiliary staff, using the World Health Organization's "My Five Moments for Hand Hygiene" tool. Covariates were explored using mixed-effects logistic regression with random department-level intercepts. Results: Hand hygiene compliance improved from 27% at baseline to 44% after 21 months. Indication/moment for HH was significantly associated with compliance. Adjusting for site, professional category and department, compliance was higher after a moment of body fluid exposure (aOR 1.43, 95% CI 1.17–1.74, p value < 0.001) and lower before an aseptic procedure (aOR 0.12, 95% CI 0.08–0.17, p value < 0.001) compared to after patient contact. Wearing of gloves often replaced proper HH in surgical departments, which although not significant, had lower compliance compared to departments for internal medicine (aOR 0.93, 95% CI 0.85–1.02). Adjusted HH compliance from all quarters improved from baseline, but comparing each quarter to the previous quarter, the improvement fluctuated over time. Conclusion: Training and mentorship on the importance of HH for all moments is needed to improve overall HH compliance. CQI with regular monitoring and feedback of HH performance can be an effective approach in improving HH compliance in public hospitals in Kenya. [ABSTRACT FROM AUTHOR]