ABSTRACT: Importance:Generating robust and timely evidence about the respiratory health risks of electronic cigarettes (e-cigarettes) is critical for informing state and federal regulatory standards for product safety. Objective:To examine the association of e-cigarette use with incident respiratory conditions, including chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma. Design, Setting, and Participants:This prospective cohort study used data from the nationally representative cohort of US adults from the Population Assessment of Tobacco and Health (PATH) study, including wave 1 from 2013 to 2014, wave 2 from 2014 to 2015, wave 3 from 2015 to 2016, and wave 4 from 2016 to 2018. Individuals aged 18 years and older at baseline with no prevalent respiratory conditions were included in the analyses. Analyses were conducted from February to July 2020. Exposures:e-Cigarette use was assessed by self-reported current use status (never, former, or current) at baseline. Main Outcomes and Measures:Incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma, as well as a composite respiratory disease encompassing all 4 conditions. Results:Among 21?618 respondents included in the analyses, 11?017 (491%) were men and 12?969 (65.2%) were non-Hispanic White. A total of 14?213 respondents were never e-cigarette users, 5076 respondents (11.6%) were former e-cigarette users, and 2329 respondents (5.2%) were current e-cigarette users. Adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, there was an increased risk of respiratory disease among former e-cigarette uses (incidence rate ratio [IRR], 1.28; 95% CI, 1.09-1.50) and current e-cigarette users (IRR, 1.31; 95% CI, 1.08-1.59). Among respondents with good self-rated health, the IRR for former e-cigarette users was 1.21 (95%CI, 1.00-1.46) and the IRR for current e-cigarette users was 1.43 (95% CI, 1.14-1.79). For specific respiratory diseases among current e-cigarette users, the IRR was 1.33 (95% CI, 1.06-1.67) for chronic bronchitis, 1.69 (95% CI, 1.15-2.49) for emphysema, 1.57 (95% CI, 1.15-2.13) for COPD, and 1.31 (95% CI, 1.01-1.71) for asthma. Conclusions and Relevance:This cohort study found that e-cigarette use was associated with an increased risk of developing respiratory disease independent of cigarette smoking. These findings add important evidence on the risk profile of novel tobacco products.