Background and Aims Currently, electronic cigarettes (e‐cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first‐ and second‐generation e‐cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e‐cigarettes.

Design Twenty‐two mildly to moderately nicotine‐dependent individuals were randomized to a cross‐over design in which they used first‐ and second‐generation e‐cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use.

Setting and participants A community‐based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.).

Measurements Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale.

Findings Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F (1, 21) = 5.057, P = 0.036, n2 P = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second‐generation compared with first‐generation e‐cigarettes.