The benefits and harms of lung cancer (LC) screening with low-dose computed tomography (LDCT) are debatable. Positive results from the US National Lung Screening Trial were not evident in the European trials, possibly due to their smaller sample sizes. To address this issue, we conducted a patient-level pooled analysis of two Italian randomized controlled trials. Data from DANTE and MILD trials were combined for a total of 3640 individuals in the LDCT arm and 2909 in the control arm. LC and overall mortality were analyzed using multivariate hazard ratios (HRs) and log-rank tests stratified by study. The median follow-up was 8.2 years, with a total of 30 480 person-years in the LDCT arm and 22 157 in the control arm. A total of 192 patients developed LC in the LDCT arm and 105 in the control arm. Half of the LC cases in the LDCT arm had stage IA or IB cancer, as compared with 21% in the control arm. Overall mortality rates/100 000 person-years were 925 in the LDCT arm and 1074 in the control arm, and LC mortality rates were 299 and 357, respectively. The multivariate pooled overall mortality HR was 0.89 (95% confidence interval: 0.74–1.06) and the LC mortality HR was 0.83 (95% confidence interval: 0.61–1.12) for the LDCT arm as compared with the control arm. The present pooled analysis shows a nonsignificant 11% reduction in overall mortality in individuals undergoing LDCT screening as compared with the control arm. A pooled analysis of all European trials would be a useful contribution to assess the real benefit of LDCT screening.