A randomized controlled trial was conducted to evaluate the efficacy of smoking cessation instruction given to general smokers at an annual physical examination. Four hundred and twenty-six male and 42 female clients were randomly assigned to an intervention group (I), and 413 males and 76 females were assigned to a control (C) group. The I group was given an approximately 2-minute smoking cessation instruction by physicians, answered a quiz concerning tobacco, chose their own behavioral goals and were handed a leaflet on how to quit smoking. Subjects in both groups responded to a self-administered questionnaire and a 6-month and 12-month follow-up was performed by post card or telephone. The I group received an encouragement card one month after instruction and abstainers of the I group were awarded a telephone card at the 6-month follow-up. The results were as follows: 1) The male I group exhibited 7.3% (6 months), 10.1% (12 months) abstinence rates and the male C group 4.4% (6 months), 5.3% (12 months), respectively. The difference in 12-month abstinence rates was statistically significant. 2) The female I group exhibited abstinence rates of 16.7% (6 months), 23.8% (12 months) and the female C group 14.5% (6 months), 17.1% (12 months), respectively. 3) A multivariate analysis of smoking cessation showed that lower nicotine dependency, strong determination for smoking cessation, and being female were significant factors for abstinence at the 6-month follow-up. At 12 months, the smoking cessation instruction also became a significant factor. These data suggest that a simple smoking cessation instruction at an annual physical examination was effective for general smokers.