Electronic cigarette (ECIG) nicotine delivery and other effects may depend on liquid nicotine concentration and user experience. This study is the first to systematically examine the influence of ECIG liquid nicotine concentration and user experience on nicotine delivery, heart rate, puff topography, and subjective effects. Thirty-three ECIG-experienced individuals and 31 ECIG-naïve cigarette smokers completed 4 laboratory conditions consisting of 2, 10-puff bouts (30-sec interpuff interval) with a 3.3-V ECIG battery attached to a 1.5-Ω “cartomizer” (7.3 W) filled with 1 ml ECIG liquid. Conditions differed by liquid nicotine concentration: 0, 8, 18, or 36 mg/ml. Participants’ plasma nicotine concentration was directly related to liquid nicotine concentration and dependent on user experience, with significantly higher mean plasma nicotine increases observed in ECIG-experienced individuals relative to ECIG-naïve smokers in each active nicotine condition. When using 36 mg/ml, mean plasma nicotine increase for ECIG-experienced individuals was 17.9 ng/ml (SD = 17.2) and 6.9 (SD = 7.1; p < .05) for ECIG-naïve individuals. Between-group differences were likely due to longer puffs taken by experienced ECIG users: collapsed across condition, mean puff duration was 5.6 sec (SD = 3.0) for ECIG-experienced and 2.9 (SD = 1.5) for ECIG-naïve individuals. ECIG use also suppressed nicotine/tobacco abstinence symptoms in both groups; the magnitude of abstinence symptom suppression depended on liquid nicotine concentration and user experience. These and other recent results suggest that policies intended to limit ECIG nicotine delivery will need to account for factors in addition to liquid nicotine concentration (e.g., device power and user behavior).