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To evaluate the effectiveness of a nurse intervention aimed at helping college student smokers quit smoking.Single-blind, pragmatic randomized controlled trial which compares a multi-component intervention, tailored specifically to college students, with a brief advice session with a 6-month follow-up.This study was conducted at the University of Navarra, Spain.A total of 255 college student smokers (age range = 18–24 years) were randomized to an intervention group (n = 133) or to a control group (n = 122).A multi-component intervention based on the Theory of Triadic Influence of Flay was developed. The intervention consisted of a 50-minute motivational interview conducted by a nurse and online self-help material. The follow-up included a reinforcing e-mail and group therapy.The primary outcome was self-reported abstinence, with biochemical verification at 6 months. The secondary outcomes consisted of the mean number of cigarettes smoked per day, self-reported attempts to quit smoking and stage of change at 6 months.At the 6-month follow-up, the smoking cessation incidence was 21.1% in the intervention group compared with 6.6% in the control group (difference = 14.5 confidence interval = 6.1–22.8; relative risk = 3.41, 95% confidence interval = 1.62–7.20). The difference in the mean number of cigarettes at 6 months was significantly different (difference = –2.2, confidence interval = –3.6 to –0.9).A multi-component intervention tailored to college students and managed by a nurse is effective in increasing smoking cessation among college students.