 This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes and finds that most studies showed no difference in respiratory parameters, indicating that ENDS substitution for smoking likely does not result in additional harm to respiratory health. However, due to the low quality of the studies, confidence in the conclusions is rated as low and robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution.