BACKGROUND: Clinical reasoning is a key competence in medicine. There is a lack of knowledge, how non-experts like medical students solve clinical problems. It is known that they have difficulties applying conceptual knowledge to clinical cases, that they lack metacognitive awareness and that higher level cognitive actions correlate with diagnostic accuracy. However, the role of conceptual, strategic, conditional, and metacognitive knowledge for clinical reasoning is unknown. METHODS: Medical students (n = 21) were exposed to three different clinical cases and instructed to use the think-aloud method. The recorded sessions were transcribed and coded with regards to the four different categories of diagnostic knowledge (see above). The transcripts were coded using the frequencies and time-coding of the categories of knowledge. The relationship between the coded data and accuracy of diagnosis was investigated with inferential statistical methods. RESULTS: The use of metacognitive knowledge is correlated with application of conceptual, but not with conditional and strategic knowledge. Furthermore, conceptual and strategic knowledge application is associated with longer time on task. However, in contrast to cognitive action levels the use of different categories of diagnostic knowledge was not associated with better diagnostic accuracy. CONCLUSIONS: The longer case work and the more intense application of conceptual knowledge in individuals with high metacognitive activity may hint towards reduced premature closure as one of the major cognitive causes of errors in medicine. Additionally, for correct case solution the cognitive actions seem to be more important than the diagnostic knowledge categories.