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Objectives: To conduct a systematic review to identify and summarize the available evidence about the effectiveness of telehealth consultations and to explore using decision modeling techniques to supplement the review. Telehealth consultations are defined as the use of telehealth to facilitate collaboration between two or more providers, often involving a specialist, or among clinical team members, across time and/or distance. Consultations may focus on the prevention, assessment, diagnosis, and/or clinical management of acute or chronic conditions., Data Sources: We searched Ovid MEDLINE ® , the Cochrane Central Register of Controlled Trials (CCRCT), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL ® ) to identify studies published from 1996 to May 2018. We also reviewed reference lists of identified studies and systematic reviews, and we solicited published or unpublished studies through an announcement in the Federal Register . Data for the model came both from studies identified via the systematic review and from other sources., Methods: We included comparative studies that provided data on clinical, cost, or intermediate outcomes associated with the use of any technology to facilitate consultations for inpatient, emergency, or outpatient care. We rated studies for risk of bias and extracted information about the study design, the telehealth interventions, and results. We assessed the strength of evidence and applicability, and then synthesized the findings using quantitative and qualitative methods. An exploratory decision model was developed to assess the potential economic impact of telehealth consultations for traumatic brain injuries in adults., Results: The search yielded 9,366 potentially relevant citations. Upon review, 8,356 were excluded and the full text of 1,010 articles was pulled for review. Of these, 233 articles met our criteria and were included—54 articles evaluated inpatient consultations; 73, emergency care; and 106, outpatient care. The overall results varied by setting and clinical topic, but generally the findings are that telehealth improved outcomes or that there was no difference between telehealth and the comparators across the settings and for the clinical indications studied. Remote intensive care unit (ICU) consultations likely reduce ICU and total hospital mortality with no significant difference in ICU or hospital length of stay; specialty telehealth consultations likely reduce the time patients spend in the emergency department; telehealth for emergency medical services likely reduces mortality for patients with heart attacks; and remote consultations for outpatient care likely improve access and a range of clinical outcomes (moderate strength of evidence in favor of telehealth). Findings with lower confidence are that inpatient telehealth consultations may reduce length of stay and costs; telehealth consultations in emergency care may improve outcomes and reduce costs due to fewer transfers, and also may reduce outpatient visits and costs due to less travel (low strength of evidence in favor of telehealth). Current evidence shows no difference in clinical outcomes with inpatient telehealth specialty consultations, no difference in mortality but also no difference in harms with telestroke consultations, and no difference in satisfaction with outpatient telehealth consultations (low strength of evidence of no difference). Too few studies reported information on potential harms from outpatient telehealth consultations for conclusions to be drawn (insufficient evidence). An exploratory cost model underscores the importance of perspective and assumptions in using modeling to extend evidence, and the need for more detailed data on costs and outcomes when telehealth is used for consultations. For example, a model comparing telehealth to transfers and in-person neurosurgical consultations for acute traumatic brain injury identified that the impact of telehealth on costs may depend on multiple factors, including how alternatives are organized (e.g., if the telehealth and in-person options are part of the same healthcare system) and whether the cost of a telehealth versus an in-person consultation differ., Conclusions: In general, the evidence indicates that telehealth consultations are effective in improving outcomes or providing services, with no difference in outcomes; however, the evidence is stronger for some applications, and less strong or insufficient for others. However, as specific details about the implementation of telehealth consultations and the environment were rarely reported, it is difficult to assess generalizability. Exploring the use of a cost model underscored that the economic impact of telehealth consultations depends on the perspective used in the analysis. The increase in both interest and investment in telehealth suggests the need to develop a research agenda that emphasizes rigor and focuses on standardized outcome comparisons that can inform policy and practice decisions.