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Investigating how e-cig aerosols behave when inhaled into the dynamic environment of the lung is important for understanding vaping-related exposure and toxicity. A ventilated artificial lung model was developed to replicate the ventilatory and environmental features of the human lung and study their impact on the characteristics of inhaled e-cig aerosols from simulated vaping scenarios. Compared to static conditions, normal breathing decreased peak particle number concentrations (PNCs) and area under the curve (AUC) by 40% and 70%, respectively, and increased particle decay rates fourfold. However, even with ventilation, intrapulmonary PNC levels exceeded 2\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> particles\/mL in a 4-puff vaping session. Both respiratory rate and tidal volume modulated e-cig aerosol exposure in a manner inversely proportional to minute ventilation. The modeled lung environment (37\u00a0\u00b0C, 88% relative humidity) also significantly altered particle size distributions by facilitating aerosol transformations such as hygroscopic growth, which further impacted e-cig aerosol exposure and particle removal. 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