Four consecutive one-month campaigns were organised to promote hand hygiene in Belgian hospitals between 2005 and 2011. The campaigns included a combination of reminders in wards, educational sessions for healthcare workers, promotion of alcohol-based hand rub use, increasing patient awareness, and audits with performance feedback. Prior and after each one month intervention period, the infection control teams measured hand hygiene compliance of healthcare workers by direct observation using a standardised observation roster. A total of 738,367 opportunities for hand hygiene were observed over the four campaigns. Compliance with hand hygiene significantly increased from 49.6% before to 68.6% after the intervention period for the first, from 53.2% to 69.5% for the second, from 58.0% to 69.1% for the third, and from 62.3% to 72.9% for the fourth campaign. The highest compliance rates were consistently observed in paediatric units. Compliance rates were always markedly lower among physicians than nurses. After patient contact and body fluid exposure risk, compliance rates were noticeably higher than before patient contact and performing aseptic procedures. We conclude that repeated countrywide campaigns to promote hand hygiene result in positive long-term outcomes. However, lower compliance rates among physicians compared with nurses, before patient contact, and before performing aseptic procedures remain challenges for future campaigns.