We aimed to explore the underlying reasons that estimates of overdiagnosis vary across and within low-dose CT (LDCT) lung cancer screening trials. We conducted a systematic review to identify estimates of overdiagnosis from randomised controlled trials of LDCT screening. We then analysed the association of Ps (the excess incidence of lung cancer as a proportion of screen-detected cases) with post-screening follow-up time using a linear random effects meta-regression model. Separately, we analysed annual Ps estimates from the US National Lung Screening Trial (NLST) and German Lung Cancer Screening Intervention Trial (LUSI) using exponential decay models with asymptotes. We conducted stratified analyses to investigate participant characteristics associated with Ps using the extended follow-up data from NLST. Among 12 overdiagnosis estimates from 8 trials, the post-screening follow-up ranged from 3.8 to 9.3 years, and Ps ranged from −27.0% (ITALUNG, 8.3y follow-up) to 67.2% (DLCST, 5.0y follow-up). Across trials, 39.1% of the variation in Ps was explained by post-screening follow-up time. The annual changes in Ps were −3.5% and −3.9% in the NLST and LUSI trials, respectively. Ps was predicted to plateau at 2.2% for NLST and 9.2% for LUSI with hypothetical infinite follow-up. In NLST, Ps increased with age from −14.9% (55–59 years) to 21.7% (70–74 years), and time trends in Ps varied by histological type. The findings suggest that differences in post-screening follow-up time partially explain variation in overdiagnosis estimates across lung cancer screening trials. Estimates of overdiagnosis should be interpreted in the context of post-screening follow-up and population characteristics.