Electronic cigarettes (ECIGs) operate by heating a nicotine-containing solution resulting in an inhalable aerosol. Nicotine delivery may be affected by users’ puffing behavior (puff topography), and little is known about the puff topography of ECIG users. The purpose of this study was to examine the extent to which a mouthpiece-based topography measurement device influences the acute effects associated with ECIG use. Twenty-nine experienced ECIG users completed two sessions differing only by the presence of a mouthpiece-based topography recording device. In both sessions, participants completed one 10 puff, 30 sec inter-puff interval (IPI) ECIG-use bout and another 90 minute ad libitum bout. Acute ECIG effects (plasma nicotine concentration, heart rate [HR], and subjective effects) were largely unaffected by the presence of the topography recording device. Evaluating ECIG puff topography through clinical laboratory methodology is necessary to understand the effects of these products (including toxicant exposure) and to inform their regulation.