Purpose: Language asymmetry between patients and providers may influence the context, content, and quality of health care communication, affecting patient outcomes and contributing to health disparities. This research examined interpreter-mediated, primary care encounters between English-speaking nurse practitioners and Spanish-speaking adult patients. Method: Situational analysis guided the collection, analysis, and interpretation of audio-recorded clinical encounter data. Results: Interpreter-mediated communication was situated within intersecting social, economic, political, and health systems contexts. Three modes of collaborative knowledge generations were Constructing Connections, Constructing Mutual Understanding, and Constructing Effective Systems Navigation Strategies. Discussion: These findings illustrate how interactants contributed individual and collective knowledge across multiple systems to address patient concerns. Conclusion: The analysis revealed ways in which communication processes may influence both providers’ diagnostic and interventional decision-making and patients’ understanding and potential compliance. Ongoing preparation and support for intraprofessional collaboration is needed to ensure effective communication and mitigate untoward effects of language asymmetries in clinical encounters.