E-cigarettes with nicotine can affect important cardiopulmonary outcomes and likely pose less risk than cigarettes, but they are not harmless. Given the existing literature, there is a need for controlled trials of e-cigarette use in populations with cardiopulmonary disease to fill the gaps between these existing examinations. Clarifying how the pulmonary and cardiac effects of e-cigarettes compare to use of conventional cigarettes in those with cardiopulmonary disease beyond single acute exposures will provide important new health information that can help inform policy.