Sputum cytological atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk.An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and seven annual screenings since enrollment. The associations between sputum cytological results from baseline screening, the first four consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model.A moderate or worse cytological result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared to negative screening results, the adjusted hazard ratios of baseline moderate or worse atypia, at least one moderate or worse atypia in the first four consecutive screening rounds during the first 10 years of follow-up were 3.11 (95%CI: 2.37-4.07), 3.25 (95%CI: 2.33-4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio=17.55, 95%CI: 8.32-37.03); atypia identified in the recent screening rounds (adjusted hazard ratio=4.14, 95%CI:2.70-6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer.Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years.Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance or chemoprevention of lung cancer.Copyright ©2021, American Association for Cancer Research.