Heart disease is the second leading cause of death in lung cancer (LC) patients, with postoperative cardiovascular disease (CVD) commonly linked to lymph node dissection (LND). This study aimed to clarify the optimal number of lymph nodes (LNs) to be dissected by investigating the impact of LND on CVD related death in patients with surgically resected non-small cell lung cancer (NSCLC). We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for a total of 154,566 patients with stage IA-IIIA NSCLC that underwent curative surgery from 2000 to 2020, and further validated using clinical data from a single-center cohort. For patients with negative lymph nodes, the optimal LND threshold was 3 without RT (SHR = 0.909, 95% CI: 0.841-0.982, p = 0.016) and 11 with RT (SHR = 0.877, 95% CI: 0.757-1.015, p = 0.079). For positive lymph nodes (PLNs), 0.53 was the structural breakpoint for the PLNs ratio (p <
0.001). Data from a single-center cohort of 200 patients showed that with LND between 10 and 12, cardiovascular events significantly increased (OR = 18.870, p = 0.044). Excessive dissection of immune-functioning LNs may contribute to the occurrence of death from heart disease and amplify the effects of RT on cardiovascular mortality.