Background and Method: Medical students are generally considered to be a unique group of experienced learners, functioning under high levels of stress and fatigue. The use of multimedia in digital environments has become a standard feature in most medical schools, but it has met with limited success. A study was designed to investigate the impact of stress and fatigue on general study resource selection, with particular interest in multimedia, and its limited uptake by medical students. A series of 58 focus groups with 107 third and fourth year medical students at the NYU School of Medicine was conducted in the spring of 2015. A survey instrument was also administered. Quantitative data analysis was conducted in SPSS-23; the qualitative data analysis was conducted through open coding and grounded theory procedures in ATLAS.ti. Findings: Results produced a model of stress and fatigue for third-year medical students, and showed a statistically significant increase in multimedia usage under fatigue but not under stress alone, and a statistically significant decline in textbook preference under conditions of stress and/or fatigue. Practice questions (i.e., "question banks") and text-based websites (evidence-based, clinical decision resources related to diagnosis and case management) were the preferred study resources under all conditions. Further analysis of the qualitative data regarding multimedia's strengths and weaknesses under stress and fatigue produced a series of 12 multimedia design and implementation factors. Discussion: While these findings are based on the specific medical student population, there may be significant implications for the general learner population, which is also confronting increased stress and fatigue. As on-line learners and other populations of learners start to look more like medical students -- trying to study when they are tired, stressed, and under severe time pressure -- it's worth considering that many of the suggestions for making multimedia resources more appealing to medical students might also have the same effects with other populations. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]