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Background and Aims: For electronic cigarettes (e‐cigarettes) to be a viable substitute for combustible cigarettes, it is likely that they must be rewarding enough for regular use, indicated by factors such as craving and dependence, important aspects of reinforcement. This study aimed to understand short‐term changes in measures of nicotine dependence between groups differing by use trajectory in a switching trial, and within group changes of these measures. Design Secondary data analysis of one arm of an e‐cigarette randomized clinical trial. Setting: San Diego, California and Kansas City, Missouri, United States. Participants: 114 African American (n = 60) and Latinx (n = 54) smokers (58.8% male) attempting to switch to nicotine salt pod system (NSPS) e‐cigarettes in a 6‐week trial. Measurements At week 6, participants were classified by use trajectory: exclusive smokers (n = 16), exclusive e‐cigarette (n = 32), or dual users (n = 66). E‐cigarette, cigarette, and total nicotine dependence (cigarette + e‐cigarette), use patterns, cigarette craving and nicotine withdrawal, and cotinine were assessed at baseline and week 6 using standard measures. Findings In between group comparisons, exclusive e‐cigarette and dual users showed greater reductions in cigarette dependence (e‐cigarette: −32.38, 95% CI = −37.7,−27.1; dual: −18.48, 95% CI = −22.2,−14.7), withdrawal (e‐cigarette: −6.25, 95% CI = −8.52,−3.98; dual: −3.18, 95% CI = −5.02,−1.34), craving (e‐cigarette: −11.44, 95% CI = −14.2,8.7; dual: −9.59, 95% CI = −11.6,−7.59), and cigarettes per day (CPD; e‐cigarette: −11.19, 95% CI = −13.1,−9.27; dual: −9.39, 95% CI = −11.3, −7.52) compared with exclusive smokers. In within group analyses, e‐cigarette and dual users showed reductions in craving and withdrawal from baseline to week 6. Exclusive e‐cigarette and dual users, maintained cotinine levels (all Ps > 0.05) and showed reductions in CPD and cigarette dependence (all Ps < 0.01). Findings were inconclusive regarding changes in total nicotine dependence from baseline to week 6 among exclusive e‐cigarette users (P = 0.123). Dual users showed increased total nicotine dependence (P < 0.001) and smokers showed decreased total dependence (P = 0.004). Conclusions: Smokers who switch to nicotine salt pod system e‐cigarettes maintain their nicotine levels and transfer their dependence, suggesting that nicotine salt pod system e‐cigarettes have a similar reinforcement potential to cigarettes and facilitate switching. [ABSTRACT FROM AUTHOR]