Objectives: The aim was to compare nursing staff compliance over the years, per health care unit, and per drug use process step. Methods: Compliance assessment was performed by nursing consultants with direct observation of the registered nurses and nursing assistants during the performance of 7 steps of the drug use process. A total of 36 compliance criteria were developed. The compliance to drug use process criteria was measured in 2007 (Prephase), 2008 (post 1), and 2011 (post 2). Totally, 10 health care units were evaluated, with a minimum of 10 doses evaluated per health care unit, including a minimum of 5 parental doses and a total of 100 nurses observed. Results: A total of 142 nurses were observed in the prephase, 140 nurses in the post 1 phase, and 98 in the post 2 phase (90% regular staff and 10% float staff). The overall compliance rates went from 77% in 2007 up to 87% in 2008 and down to 78% in 2011. Conclusions: This cross-sectional observational study revealed a significant difference in the drug use process compliance in terms of drug preparation and drug administration for inpatients at the bedside, between 2007 and 2011.