There is a major gap in educational best-practices regarding how to scholastically foster diagnostic accuracy among Nurse Practitioner (NP) students. This research establishes foundational information that will lead to evidenced-based educational interventions and curricular changes leveraging the technique of self-explanation in order to increase NP diagnostic accuracy. Self-explanation is defined as generating explanations for oneself while problem-solving, in attempts to make sense of new information. Because different types of self-explanations enhance learning to varying degrees, identifying high quality ways of self-explaining present among successful NP student diagnosticians is a critical step in advancing diagnostic reasoning education. In this mixed methods content analysis study, NP students were asked to solve written case studies while self-explaining out loud. Self-explanations were analyzed both qualitatively and quantitatively.The initial research question of this study was: How do NP students self-explain during diagnostic reasoning? Using iterative, qualitative analysis techniques, 17 categories of NP student diagnostician self-explanation emerged. Inference self-explanations include both clinical and biological foci. Non-inference self-explanations monitor students' understanding of clinical data, and reflect shallow information processing. Two research aims sought to quantitatively explore qualitative findings. Aim one was to compare differences between student expertise levels in terms of diagnostic accuracy scores and self-explanation scores. Expert students self-explain in qualitatively different ways than novice students, utilizing more biological and clinical inference self-explanations and less non-inferences statements. Groups did not significantly differ in terms of diagnostic accuracy (p<0.1636). Aim two was to explore relationships among ways of self-explaining and diagnostic accuracy levels. Clinical inferences were not significantly associated with levels of diagnostic accuracy (p<0.39). Biological inference scores were, however, significantly associated with diagnostic accuracy scores, r(35)=0.49 (p<0.002).Collectively, these findings provide a solid framework for NP educators to support diagnostic accuracy among students via self-explanation. Prompted self-explanation interventions and curriculum changes integrating disease state courses and human sciences will encourage students to self-explain clinical features in terms of underlying biology. Cultivating the momentum created by this research will, ultimately, mitigate a major issue in today's healthcare system through promotion of accurate diagnoses and patient well-being. [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.]