Efficient hand hygiene is essential for preventing the transmission of microorganisms. Alcohol-based hand rub (ABHR) is a recommended method. We compared health personnel (skilled nurse students) with random adults to study the effect of an ABHR procedure. A water-based hand rub (WBHR) procedure, using running tap water and a hand-drying machine, was also investigated. The study included 27 nurse students and 26 random adults. Hands were contaminated with Escherichia coli, and concentrations of colony forming units (CFU/mL) were determined before and after ABHR or WBHR. Concentrations after ABHR were 1537 CFU/mL (nurse students) and 13,508 CFU/mL (random adults) (p < 0.001). One-third of participants reported skin irritation from daily ABHR. Concentrations after WBHR were 41 CFU/mL (nurse students) and 115 CFU/mL (random adults) (p < 0.011). The majority of participants (88.5%) preferred the WBHR method. Results from 50 air samples from filtered air from the hand dryer outlet showed no CFU in 47 samples. A significant difference between the two groups was shown for the ABHR method, indicating that training skills are important for efficient hand hygiene. Surprisingly, the WBHR method seemed to have a significant effect in largely removing transient bacteria from hands.