This study aimed to compare the outcomes and cost differences between primary lung cancer (PLC) and second primary lung cancer (SPLC) patients who underwent video-assisted thoracoscopic surgery (VATS). This was a retrospective analysis of 124 patients with lung cancer stages I, II, and III who underwent VATS between January 2018 and January 2023. The patients were divided into two groups based on their cancer status that was matched by age and gender: the PLC group (n= 62) and the SPLC group (n= 62). The results showed that there was no significant difference in the clinical characteristics between the 2 groups, except for the Charlson Comorbidity Index (CCI), with a score above 3 in 62.9% of PLC patients and 80.6% among SPLC patients (p= 0.028). Regarding the surgical outcomes, the operative time for the VATS intervention was significantly higher in the SPLC group, with a median of 300 min, compared with 260 min in the PLC group (p= 0.001), varying by the cancer staging as well. The average duration of hospitalization was significantly longer before and after surgery among patients with SPLC (6.1 days after surgery), compared with 4.2 days after surgery in the PLC group (0.006). Regarding the cost analysis, the total hospitalization cost was significantly higher in the SPLC group (15,400 RON vs. 12,800 RON;p= 0.007). Lastly, there was a significant difference in the survival probability between the two patient groups (log-rankp-value = 0.038). The 2-year survival was 41.9% among PLC patients and only 24.2% among those with SPLC. At the 5-year follow-up, there were only 1.6% survivors in the SPLC group, compared with 11.3% in the PLC group (p-value = 0.028). In conclusion, this study found that VATS is a safe and effective surgical approach for both PLC and SPLC patients. However, SPLC patients have a higher VATS operating time and require more healthcare resources than PLC patients, resulting in higher hospitalization costs. These findings suggest that careful pre-operative evaluation and individualized surgical planning are necessary to optimize the outcomes and cost-effectiveness of VATS for lung cancer patients. Nevertheless, the 5-year survival remains very low and concerning.