BACKGROUND: Human connection is at the heart of medical care, but questions remain as to the effectiveness of interpersonal interventions. The purpose of this review was to characterize the associations between patient-provider interpersonal interventions and the quadruple aim outcomes (population health, patient experience, cost, and provider experience). n METHODS: We sourced data from PubMed, EMBASE, and PsycInfo (January 1997-August 2017). Selected studies included randomized controlled trials and controlled observational studies that examined the association between patient-provider interpersonal interventions and at least one outcome measure of the quadruple aim. Two abstractors independently extracted information about study design, methods, and quality. We characterized evidence related to the objective of the intervention, type and duration of intervention training, target recipient (provider-only vs. provider-patient dyad), and quadruple aim outcomes. n RESULTS: Seventy-three out of 21,835 studies met the design and outcome inclusion criteria. The methodological quality of research was moderate to high for most included studies; 67% of interventions targeted the provider. Most studies measured impact on patient experience; improvements in experience (e.g., satisfaction, patient-centeredness, reduced unmet needs) often corresponded with a positive impact on other patient health outcomes (e.g., quality of life, depression, adherence). Enhanced interpersonal interactions improved provider well-being, burnout, stress, and confidence in communicating with difficult patients. Roughly a quarter of studies evaluated cost, but the majority reported no significant differences between intervention and control groups. Among studies that measured time in the clinical encounter, intervention effects varied. Interventions with lower demands on provider time and effort were often as effective as those with higher demands. n DISCUSSION: Simple, low-demand patient-provider interpersonal interventions may have the potential to improve patient health and patient and provider experience, but there is limited evidence that these interventions influence cost-related outcomes.