Background: Clinical reasoning is essential to medical practice, but because it entails internal mental processes, it is difficult to assess. Functional magnetic resonance imaging (fMRI) and think-aloud protocols may improve understanding of clinical reasoning as these methods can more directly assess these processes. The objective of our study was to use a combination of fMRI and think-aloud procedures to examine fMRI correlates of a leading theoretical model in clinical reasoning based on experimental findings to date: analytic (i.e., actively comparing and contrasting diagnostic entities) and nonanalytic (i.e., pattern recognition) reasoning. We hypothesized that there would be functional neuroimaging differences between analytic and nonanalytic reasoning theory. Methods: 17 board-certified experts in internal medicine answered and reflected on validated U.S. Medical Licensing Exam and American Board of Internal Medicine multiple-choice questions (easy and difficult) during an fMRI scan. This procedure was followed by completion of a formal think-aloud procedure. Results: fMRI findings provide some support for the presence of analytic and nonanalytic reasoning systems. Statistically significant activation of prefrontal cortex distinguished answering incorrectly versus correctly (p < 0.01), whereas activation of precuneus and midtemporal gyrus distinguished not guessing from guessing (p<0.01). Conclusions: We found limited fMRI evidence to support analytic and nonanalytic reasoning theory, as our results indicate functional differences with correct vs. incorrect answers and guessing vs. not guessing. However, our findings did not suggest one consistent fMRI activation pattern of internal medicine expertise. This model of employing fMRI correlates offers opportunities to enhance our understanding of theory, as well as improve our teaching and assessment of clinical reasoning, a key outcome of medical education.