This research investigated the overall mortality and lung cancer (LC) survival differences between females and males undergoing lung cancer screening (LCS), with emphasis on the predictive significance of coronary artery calcification (CAC) at the initial low-dose computed tomography (LDCT). Analyzing data from 6495 heavy smokers from MILD and BioMILD LCS trials (2005-2016), the study found that 12-year all-cause mortality rates were significantly lower in females (4.1%) than males (7.7%). Females also had better LC survival rates post-diagnosis and a lower median CAC score (8.7 vs. 41 in males). The rise in CAC scores was directly proportional to increased mortality in both sexes. Despite similar LC incidence, females displayed lower LC mortality and better survival rates. The AI-based software, AVIEW (Coreline Soft, Seoul, Korea), was employed to automatically calculate CAC scores on LDCT images, suggesting women's lower CAC might elucidate their better survival and reduced mortality rates.