Background Reliable assessment of suicide and self-harm risk in emergency medicine is critical for effective intervention and treatment of patients affected by mental health disorders. Teams of clinicians face the challenge of rapidly integrating medical history, wide-ranging psychosocial factors, and real-time patient observations to inform diagnosis, treatment, and referral decisions. Patient outcomes therefore depend on the reliable flow of information through networks of clinical staff and information systems. This study aimed to develop a quantitative data-driven research framework for the analysis of information flow in emergency healthcare settings to evaluate clinical practice and operational models for emergency psychiatric care. Methods and findings We deployed 2 observers in a tertiary hospital emergency department during 2018 for a total of 118.5 h to record clinical interactions along patient trajectories for presentations with risk of self-harm or suicide (n = 272 interactions for n = 43 patient trajectories). The study population was reflective of a naturalistic sample of patients presenting to a tertiary emergency department in a metropolitan Australian city. Using the observational data, we constructed a clinical interaction network to model the flow of clinical information at a systems level. Community detection via modularity maximization revealed communities in the network closely aligned with the underlying clinical team structure. The Psychiatric Liaison Nurse (PLN) was identified as the most important agent in the network as quantified by node degree, closeness centrality, and betweenness centrality. Betweenness centrality of the PLN was significantly higher than expected by chance (>95th percentile compared with randomly shuffled networks) and removing the PLN from the network reduced both the global efficiency of the model and the closeness centrality of all doctors. This indicated a potential vulnerability in the system that could negatively impact patient care if the function of the PLN was compromised. We developed an algorithmic strategy to mitigate this risk by targeted strengthening of links between clinical teams using greedy cumulative addition of network edges in the model. Finally, we identified specific interactions along patient trajectories which were most likely to precipitate a psychiatric referral using a machine learning model trained on features from dynamically constructed clinical interaction networks. The main limitation of this study is the use of nonclinical information only (i.e., modeling is based on timing of interactions and agents involved, but not the content or quantity of information transferred during interactions). Conclusions This study demonstrates a data-driven research framework, new to the best of our knowledge, to assess and reinforce important information pathways that guide clinical decision processes and provide complementary insights for improving clinical practice and operational models in emergency medicine for patients at risk of suicide or self-harm. Our findings suggest that PLNs can play a crucial role in clinical communication, but overreliance on PLNs may pose risks to reliable information flow. Operational models that utilize PLNs may be made more robust to these risks by improving interdisciplinary communication between doctors. Our research framework could also be applied more broadly to investigate service delivery in different healthcare settings or for other medical specialties, patient groups, or demographics.