One of the most critical functions of a nurse is the safe administration of medications. To ensure patient safety, nurses must be competent in medication dosage calculation (MDC) skills. It is imperative that nursing educators discover the most effective teaching methodology to ensure the greatest level of competency in MDC skills. The purpose of this causal-comparative quantitative study was to compare the effects of two teaching methodologies on senior-level nursing students’ completion of program MDC requirements, mathematics self-efficacy, and MDC competency at program end. The sample consisted of 94 senior-level bachelor’s degree nursing students from a southeastern United States university in the spring of 2015. Each participant completed a demographic questionnaire, Mathematics Self-Efficacy Scale (MSES), and MDC competency exam. Participants were assigned to one of two groups based on whether the participants completed MDC education in a stand-alone course or throughout the curriculum through self-learning modules. Chi-square and independent t-test results indicated that there were no statistical differences between the two groups (stand-alone course vs. self-learning modules) and ability to complete program MDC requirements, MSES scores, and MDC competency exam scores at program end. Data analysis using Chi-square and Fisher’s Exact tests indicated a statistically significant, but weak, correlation between MSES scores and MDC competency exam scores. Findings from this study indicate teaching MDC to nursing students using a stand-alone course versus self-learning modules produces the same results in the students’ ability to complete program MDC requirements, mathematics self-efficacy, and MDC competency at program end.