The aerosol produced from electronic cigarettes (ECs) is significantly less complex and contains far fewer toxicants than combustible cigarette (CC) smoke. Limited work to date has explored changes in biomarkers of combustion-derived toxicants after smokers switch to ECs. We present results from a randomized, parallel group clinical study that enrolled current smokers to switch to an EC or nicotine gum while in clinic. Subjects smoked their usual brand CCs ad libitum during a baseline period, after which they were randomized to ad libitum use of either a VUSE EC (Original or Menthol) or 4 mg nicotine gum for five days. Biomarkers of 23 toxicants typically associated with CC smoking were measured in 24-hour urine samples, plasma, and whole blood collected at baseline and on Day 5 following product switch. Average total nicotine equivalents decreased ~38% among smokers switched to an EC and decreased ~62% among smokers switched to gum. Average non-nicotine biomarker levels decreased approximately 30-99% in subjects switched to an EC. Furthermore, these decreases were similar to the decreases observed in subjects switched to nicotine gum. The biomarker results presented here demonstrate that subjects switched to ECs and subjects switched to nicotine gum have comparably reduced exposure to cigarette smoke toxicants. Nicotine exposure is also reduced in both groups, but to a lesser extent among those subjects switched to ECs.