Objective The goal of the current study was to empirically compare successive cohorts of treatment-seeking smokers who enrolled in randomised clinical trials in a region of the USA characterised by strong tobacco control policies and low smoking prevalence, over the past three decades.

Design Retrospective treatment cohort comparison.

Setting Data were collected from 9 randomised clinical trials conducted at Stanford University and the University of California, San Francisco, between 1990 and 2013.

Participants Data from a total of 2083 participants were included (Stanford, n=1356; University of California San Francisco, n=727).

Primary and secondary outcomes One-way analysis of variance and covariance, χ² and logistic regression analyses were used to examine relations between nicotine dependence, cigarettes per day, depressive symptoms and demographic characteristics among study cohorts.

Results Similar trends were observed at both settings. When compared to earlier trials, participants in more recent trials smoked fewer cigarettes, were less nicotine-dependent, reported more depressive symptoms, were more likely to be male and more likely to be from a minority ethnic/racial group, than those enrolled in initial trials (all p's<0.05). Analysis of covariances revealed that cigarettes per day, nicotine dependence and current depressive symptom scores were each significantly related to trial (all p's<0.001).

Conclusions Our findings suggest that more recent smoking cessation treatment-seeking cohorts in a low prevalence region were characterised by less smoking severity, more severe symptoms of depression and were more likely to be male and from a minority racial/ethnic group.