Cigarette smoking is associated with chronic obstructive pulmonary disease and chronic bronchitis. Acquired ion transport abnormalities, including CFTR dysfunction, caused by cigarette smoking have been proposed as potential mechanisms for mucus obstruction in chronic bronchitis. Although popular and perceived to be safe, it remains unclear if e-cigarette use harms the airways via mechanisms altering ion transport. Here, we sought to determine if e-cigarette vapor, like cigarette smoke, had the potential to induce acquired CFTR dysfunction, and to what degree. Electrophysiologic methods demonstrated reduced chloride transport caused by vaporized e-cigarette liquid or vegetable glycerin at various exposures (30 min: 57.2% and 14.4% respectively, vs. control, p<0.0001), but not by unvaporized liquid (60 min: 17.6% vs. untreated), indicating that thermal degradation of these products is required to induce the observed defects. We also observed reduced ATP-dependent responses (-10.8±3.0 vs. -18.8±5.1 µA/cm2 control) and ENaC activity (95.8% reduction) in primary HBE cells after 5 min, suggesting exposures dramatically inhibit epithelial ion transport beyond CFTR, even without diminished transepithelial resistance or cytotoxicity. Vaporizing e-cigarette liquid produced reactive aldehydes including acrolein (shown to induce acquired CFTR dysfunction), as quantified by mass spectrometry, demonstrating that respiratory toxicants in cigarette smoke can also be found in e-cigarette vapor (30 min: air 224.5±15.99, unvaporized liquid 284.8±35.03, vapor 54,468±3908 ng/mL, p<0.0001). E-cigarettes can induce ion channel dysfunction in airway epithelial cells, partly through acrolein production. These findings indicate a heretofore unknown toxicity of e-cigarette use known to be associated with chronic bronchitis onset and progression, and COPD severity.