For patients, hospital emergency departments (EDs) are unfamiliar, institutional contexts involving high-stakes communication in heightened emotional circumstances. This study examines laughter, as one expression of emotion, in an existing 649,631-word corpus of naturally occurring clinician-patient interactions recorded in five Australian hospitals. A mixed methods approach revealed (1) the spread, frequency and producers of laughter, and (2) the functions of laughter in unfolding interactional contexts. First, a corpus analysis showed that laughter in the ED was most frequently produced by nurses and patients, but relatively infrequently by doctors. Secondly, two case studies comprising all the interactions of two patients for the whole duration of their ED visits were analysed in detail to explore the individuals’ contrasting patterns of laughter. The analysis revealed how laughter can be a cue to the affective dynamics of patient-clinician interactions about serious matters, for example, signalling difficult topics and managing anxiety in the ED context. Laughter, and any related humour, can indicate the achievement of mutuality, which is considered a cornerstone of genuine shared decision-making and patient participation in their own care. Therefore, the findings suggest that a sensitive responsiveness to patient-initiated laughter, and any associated humour, may promote patient-centred relationships in clinical interactions.