Background: The current approach to measuring hand hygiene (HH) relies on human auditors who capture <1% of HH opportunities and rapidly become recognized by staff, resulting in inflation in performance. Our goal was to assess the impact of group electronic monitoring coupled with unit-led quality improvement on HH performance and prevention of healthcare-associated transmission and infection. Methods: A stepped-wedge cluster randomized quality improvement study was undertaken across 5 acute-care hospitals in Ontario, Canada. Overall, 746 inpatient beds were electronically monitored across 26 inpatient medical and surgical units. Daily HH performance as measured by group electronic monitoring was reported to inpatient units who discussed results to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (%) between baseline and intervention. Secondary outcomes included transmission of antibiotic resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. Results: After adjusting for the correlation within inpatient units, there was a significant overall improvement in HH adherence associated with the intervention (IRR, 1.73; 95% CI, 1.47–1.99; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1,395,450 of 4,544,144) to 37% (598,035 of 1,536,643) within 1 month, followed by consecutive incremental increases up to 53% (804,108 of 1,515,537) by 10 months (P < .0001). We identified a trend toward reduced healthcare-associated transmission of MRSA (0.74; 95% CI, 0.53–1.04; P = .08). Conclusions: The introduction of a system for group electronic monitoring led to rapid, significant, and sustained improvements in HH performance within a 2-year period.