Collaborative skills are crucial in knowledge-rich domains, such as medical diagnosing. The Collaborative Diagnostic Reasoning (CDR) model emphasizes the importance of high-quality collaborative diagnostic activities (CDAs; e.g., evidence elicitation and sharing), influenced by content and collaboration knowledge as well as more general social skills, to achieve accurate, justified, and efficient diagnostic outcomes (Radkowitsch et al., 2022). However, it has not yet been empirically tested, and the relationships between individual characteristics, CDAs, and diagnostic outcomes remain largely unexplored. The aim of this study was to test the CDR model by analyzing data from three studies in a simulation-based environment and to better understand the construct and the processes involved (N = 504 intermediate medical students) using a structural equation model including indirect effects. We found various stable relationships between individual characteristics and CDAs, and between CDAs and diagnostic outcome, highlighting the multidimensional nature of CDR. While both content and collaboration knowledge were important for CDAs, none of the individual characteristics directly related to diagnostic outcome. The study suggests that CDAs are important factors in achieving successful diagnoses in collaborative contexts, particularly in simulation-based settings. CDAs are influenced by content and collaboration knowledge, highlighting the importance of understanding collaboration partners’ knowledge. We propose revising the CDR model by assigning higher priority to collaboration knowledge compared with social skills, and dividing the CDAs into information elicitation and sharing, with sharing being more transactive. Training should focus on the development of CDAs to improve CDR skills.