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Introduction: Medication errors are risk factors for patients’ health and may have irrecoverable effects. These errors include medication miscalculations by nurses and nursing students. This study aimed to design a multimedia application in the field of education for drug calculations in order to compare its effectiveness with the lecture method. Methods: This study selected 82 nursing students of Tabriz University of Medical Sciences in their second and third semesters in 2015. They were pre-tested by a researcher-made multiple-choice questionnaire on their knowledge of drug administration principles and ability to carry out medicinal calculations before training and were then divided through a random block design into two groups of intervention (education with designed software) and control (lecturing) based on the mean grade of previous semesters and the pre-test score. The knowledge and ability post-test was performed using the same questions after 4 weeks of training, and the data were analyzed with IBM SPSS 20 using independent samples t-test, paired-samples t-test, and ANCOVA. Results: Drug calculation ability significantly increased after training in both the control and experimental groups (p<0.05). However, no significant difference emerged between the two groups in terms of medicinal calculation ability after training (p>0.05). The results showed that both training methods had no significant effect on study participants’ knowledge of medicinal principles (p>0.05), whereas the score of knowledge of medicinal principles in the control group increased non-significantly. The results of the Kolmogorov-Smirnov test show that, since p>0.05, the data in the variable of knowledge of drug prescription principles and ability of medicinal calculations had a normal distribution. Conclusion: The use of educational software has no significant effect on nursing students’ drug knowledge or medicinal calculation ability. However, an e-learning program can reduce the lecture time and cost of repeated topics, such as medication, suggesting that it can be an effective component in nurse education programs