Smoking cigarettes is the most preventable cause of death in the US. Smokers are often unsuccessful at quitting because they are dependent. Reducing nicotine could be one way to reduce dependence. Currently, reducing cigarettes per day (CPD) is the most common strategy to reduce nicotine intake. However, some have proposed switching to very low nicotine content (VLNC) cigarettes to reduce nicotine and dependence. Both reducing CPD and switching to VLNC cigarettes aim to reduce nicotine but do so in different ways. I conducted a randomized trial to compare the degree to which switching to VLNC cigarettes vs reducing CPD 1) is more acceptable and 2) decreases dependence more among smokers not ready to quit. Sixty-eight adult smokers of [greater than or equal to] 10 cigarettes/day who were not ready to quit smoked full nicotine study cigarettes ad-lib for 1 week (week 0). I provided all participants with nicotine replacement therapy (NRT) patches and instructions to gradually reduce over the next 4 weeks by either 1) switching to lower nicotine content VLNC cigarettes or 2) reducing the number of full nicotine CPD. I provided VLNC participants with their usual number of cigarettes throughout the study but cigarettes contained only 70% of their usual nicotine at week 1, 35% at week 2, 15% at week 3, and 3% at week 4. I provided CPD participants with full nicotine cigarettes throughout the study but only 70% of their usual number of cigarettes at week 1, 35% at week 2, 15% at week 3, and 3% at week 4. I instructed participants to attempt to smoke only study cigarettes and report use of all (study + non-study) cigarettes via nightly surveys. I used participants' percent non-study cigarettes/day as a proxy for acceptability and the Nicotine Dependence Syndrome Scale as my primary measure of dependence. Participants completed self-report measures and provided breath and urine samples at weekly visits during the 5-week study period. I tested between-group differences, within-participant change over time, and group by time interactions using multi-level modeling. Switching to VLNC cigarettes was more acceptable than reducing CPD (F=5.0 p<.05). Acceptability declined over time for CPD participants as they were instructed to reduce more nicotine (F=42.2, p<.001) but this was not true for VLNC participants (F=29.5, p<.001). Dependence declined over time for both VLNC (F=10.5, p<001) and CPD (F=5.0, p<.01) participants but declined more over time for VLNC than CPD participants (F=3.2, p<.05). This is the first trial to directly compare switching to VLNC cigarettes vs reducing CPD. Large reductions were more acceptable and effective at decreasing dependence among participants who switched to VLNC cigarettes than those who reduced CPD when all were aided by NRT. My findings suggest that regulatory policy that promotes a gradual transition to VLNC cigarettes could be more acceptable and effective at decreasing dependence than the common strategy of reducing CPD. Furthermore, NRT-aided transitions to VLNC cigarettes could be a useful and acceptable component for clinical interventions to reduce nicotine dependence among smokers not ready to quit and thereby make it more likely for smokers to quit and succeed.