Background Current smokers are at risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development. Methods We conducted a population-based cohort study using the National Health Insurance Service database in South Korea. Of the 10,490,491 subjects who underwent health check-up from January 1, 2009 to December 31, 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until December 31, 2017. We divided all study participants into the following 3 groups: never, former, and current smokers. The primary endpoint was newly developed TB. Results Among 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (aHR 1.158; 95% CI 1.131-1.186), and the association was strengthened with increasing amount and duration of smoking. The risk of TB development was significantly lower in former smokers than in never smokers (aHR 0.947; 95% CI 0.921-0.973), especially in those with fewer than 1 pack per day of smoking amount or 30 years of smoking duration. Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.795; 95% CI 0.723-0.874). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development (aHR 1.351; 95% CI 1.094- 1.670). Conclusions Our findings suggest that smoking cessation may be associated with decreased risk of TB development. Furthermore, weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development.