Introduction We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. Methods We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. Results At entry, smoking prevalence was 15.4%in healthy participants, 29.8%with COPD, 15.8%with asthma, 21.7%with diabetes mellitus, 17.2%with ischemic heart disease/heart failure and 18.6%in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2%versus 27.7%in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95%CI: 1.61-3.42), new diagnosis of asthma (OR=1.84, 95%CI: 1.18-2.90) and low number of pack-years. Conclusions Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support.