This paper explores the role that self-regulation and emotions play in establishing a clinical diagnosis in the context of solving a clinical case in BioWorld, a computer supported learning environment designed for medical students to practice clinical reasoning. Group differences between high and low performers were explored. The results revealed no group differences in overall measures of SRL but high performers spend more time than lows in a subcategory of the reflection phase (reflecting on prioritized evidence and results). A reciprocal role of emotions was demonstrated for clinical reasoning and predicted students' diagnostic performance. High performers showed less negative activating emotions than low performers.