Background: Prehospital assessments are complex and may be influenced by biases. Improving clinical reasoning and decision-making is important for patient safety. When assessing nurses' performance, surveys or observer-based tools are often used. To our knowledge, there are no tools based on clinical outcomes, triangulating both the reasoning process and the decision-making. This study aimed to assess nurse specialists’ clinical reasoning and decision-making, using a novel assessment model, and to investigate the effect of the metacognitive TWED mnemonic. Methods: The study had mixed methods, experimental crossover design. Thirteen nurse specialists performed two patient cases in a simulation setting that induced biases, with groups switching cases after receiving brief training on a self-initiated metacognitive mnemonic. Primary outcomes were point-based scoring on clinical decision-making, grading of potential risks of patient harm, and analysis of clinical reasoning through written reflections. Results: Clinical reasoning and decision-making varied between the cases and among the participants, with no overall group or demographic differences. Regarding the patient case with most biases induced, the decision-making in one out of three assessments posed moderate to high potential risks of patient harm. In this case, the internal consistency of the overall model was good, whereas the different parts of the model could explain divergence in the other case. Qualitative analysis revealed an inability to handle conflicting data, as linked to limited reasoning and decision-making. The mnemonic increased the number of differential diagnoses, but slightly decreased performance on all primary outcomes. Conclusions: Within this study setting, nurse specialists were sensitive to biases, resulting in assessments posing risks of potential patient harm. The novel assessment model showed promise in triangulation, while assessing clinical outcomes. The mnemonic had a potential negative impact on both clinical reasoning and decision-making.