Proportional reasoning is the basis for most medication calculation processes and is fundamental for high-quality care and patient safety. We designed a simulated Medication Mathematics (siMMath) environment to support proportional reasoning in transitioning via concreteness fading between two mediators. The first mediator is simulated nursing tools of medication preparation. The second is a ratio-table setup which is used as a goal representation, which enables one to spatially hold in place different quantities in their relative proportion. We conducted a two-part study with nursing students. Part 1 was a quasi-experimental pretest-intervention-posttest design assessing the effectiveness of learning, by evaluating four categories of medical calculation questionnaire items (solid medications, unit conversion, concentrations, infusion rates). We used the Noelting proportional reasoning test to evaluate the generalizability and abstraction of proportional reasoning. Part 1 included an experimental group (n = 96) learning with siMMath, and a comparison group (n = 73) learning with an equation-based lecture approach. Part 2 employed a case study design to characterize the learning process. The experimental group's learning gains were significantly higher than the comparison group's for the two most challenging categories of the medication calculation problems questionnaire, namely concentrations and infusion rates. Furthermore, the experimental group's learning gains were significantly higher than the comparison group's for formal operational reasoning on the Noelting test. Students who used a ratio-table setup scored significantly higher on the Noelting posttest questionnaire. Nursing students who learned with the siMMath environment overcame difficulties in proportional reasoning to the highest levels and extended this understanding to other contexts.