Electronic nicotine delivery systems (ENDS) were evaluated in a randomized controlled trial to assess their effectiveness in smoking cessation compared to standard-of-care (SOC) counseling. The study enrolled 1246 adult smokers who were randomized to either receive ENDS and e-liquids along with SOC counseling or to receive SOC counseling alone. The primary outcome was biochemical validation of continuous tobacco smoking abstinence at 6 months, with 28.9% of the intervention group and 16.3% of the control group achieving abstinence. Secondary outcomes included sustained abstinence, 7-day point prevalence abstinence, and adverse events. The intervention group showed higher abstinence rates, though nicotine use through ENDS or NRT was also higher. Adverse events were more common in the intervention group, but serious adverse events were similar between groups. The study found that adding ENDS to SOC counseling increased tobacco abstinence more than SOC alone. The trial was well-powered and followed rigorous methods for data collection and analysis. The results suggest that ENDS could be a viable option for smokers seeking to quit tobacco without necessarily avoiding nicotine. However, the study had limitations, including unblinded group allocation and potential overestimation of abstinence rates due to missing data. The findings support the use of ENDS in smoking cessation programs, but further research is needed to confirm long-term effectiveness and safety. The study was funded by several Swiss organizations and had no industry involvement.Electronic nicotine delivery systems (ENDS) were evaluated in a randomized controlled trial to assess their effectiveness in smoking cessation compared to standard-of-care (SOC) counseling. The study enrolled 1246 adult smokers who were randomized to either receive ENDS and e-liquids along with SOC counseling or to receive SOC counseling alone. The primary outcome was biochemical validation of continuous tobacco smoking abstinence at 6 months, with 28.9% of the intervention group and 16.3% of the control group achieving abstinence. Secondary outcomes included sustained abstinence, 7-day point prevalence abstinence, and adverse events. The intervention group showed higher abstinence rates, though nicotine use through ENDS or NRT was also higher. Adverse events were more common in the intervention group, but serious adverse events were similar between groups. The study found that adding ENDS to SOC counseling increased tobacco abstinence more than SOC alone. The trial was well-powered and followed rigorous methods for data collection and analysis. The results suggest that ENDS could be a viable option for smokers seeking to quit tobacco without necessarily avoiding nicotine. However, the study had limitations, including unblinded group allocation and potential overestimation of abstinence rates due to missing data. The findings support the use of ENDS in smoking cessation programs, but further research is needed to confirm long-term effectiveness and safety. The study was funded by several Swiss organizations and had no industry involvement.