In this controlled before-after study the effect of improvements, derived from Lean Six Sigma strategy, on parenteral medication administration errors and the potential risk of harm was determined. During baseline measurement, on control versus intervention ward, at least one administration error occurred in 14 (74%) and 6 (46%) administrations with potential risk of harm in 6 (32%) and 1 (8%) administrations. Most administration errors with high potential risk of harm occurred in bolus injections: 8 (57%) versus 2 (67%) bolus injections were injected too fast with a potential risk of harm in 6 (43%) and 1 (33%) bolus injections on control and intervention ward. Implemented improvement strategies, based on major causes of too fast administration of bolus injections, were: Substitution of bolus injections by infusions, education, availability of administration information and drug round tabards. Post intervention, on the control ward in 76 (76%) administrations at least one error was made (RR 1.03; CI95:0.77-1.38), with a potential risk of harm in 14 (14%) administrations (RR 0.45; CI95:0.20-1.02). In 40 (68%) administrations on the intervention ward at least one error occurred (RR 1.47; CI95:0.80-2.71) but no administrations were associated with a potential risk of harm. A shift in wrong duration administration errors from bolus injections to infusions, with a reduction of potential risk of harm, seems to have occurred on the intervention ward. Although data are insufficient to prove an effect, Lean Six Sigma was experienced as a suitable strategy to select tailored improvements. Further studies are required to prove the effect of the strategy on parenteral medication administration errors.