Nurses need to be competent and confident in performing drug calculations to ensure patient safety. The purpose of this study is to compare an interactive e-drug calculations package, developed using Cognitive Load Theory as its theoretical framework, with traditional handout learning support on nursing students' drug calculation ability, self-efficacy and support material satisfaction.A cluster randomised controlled trial comparing the e-package with traditional handout learning support was conducted with a September cohort (n=137) and a February cohort (n=92) of second year diploma nursing students. Students from each cohort were geographically dispersed over 3 or 4 independent sites.Students from each cohort were invited to participate, halfway through their second year, before and after a 12 week clinical practice placement. During their placement the intervention group received the e-drug calculations package while the control group received traditional 'handout' support material. Drug calculation ability and self-efficacy tests were given to the participants pre- and post-intervention. Participants were given the support material satisfaction scale post-intervention.Students in both cohorts randomised to e-learning were more able to perform drug calculations than those receiving the handout (September: mean 48.4% versus 34.7%, p=0.027; February: mean 47.6% versus 38.3%, p=0.024). February cohort students using the e-package were more confident in performing drug calculations than those students using handouts (self-efficacy mean 56.7% versus 45.8%, p=0.022). There was no difference in improved self-efficacy between intervention and control for students in the September cohort. Students who used the package were more satisfied with its use than the students who used the handout (mean 29.6 versus 26.5, p=0.001), particularly with regard to the package enhancing their learning (p=0.023), being an effective way to learn (p=0.005), providing practice and feedback (p<0.001), being accessible (p=0.027), user friendly (p=0.02) and providing learning enjoyment (p=0.022).It is essential that nurses are educated and supported to become, and remain, confident and competent in performing drug calculations. This study found the e-drug calculations package, based on Cognitive Load Theory, to be significantly more effective than a handout in improving students' drug calculation ability and self-efficacy, with students who used the package being significantly more satisfied with its use than students who used the handout. This package could particularly be useful for the continuing professional development of any healthcare professional involved in drug calculations.