Video-assisted thoracoscopic surgery (VATS) is considered the standard procedure for surgical resection in non-small-cell lung cancer (NSCLC). However, there is still lingering speculation on its adequacy of lymph node (LN) dissection or sampling and the long-term survival benefits when compared to open thoracotomy. Given the above, we conducted a systematic review comparing VATS and thoracotomy in terms of their oncological effectiveness in resection. We explored major research literature databases and search engines such as MEDLINE, PubMed, PubMed Central, Google Scholar, and ResearchGate to find pertinent articles. After the meticulous screening, quality check, and applying relevant filters according to our eligibility criteria, we identified 16 studies relevant to our research question, out of which one was a randomized controlled trial, one meta-analysis, and 14 were observational studies. The study comprised 44,673 patients with NSCLC, out of whom 15,093 patients were operated by VATS and the remaining 29,580 patients by thoracotomy. The results indicate that VATS is equivalent to thoracotomy in total LNs (N1 + N2) and LN stations dissected. However, a thoracotomy may achieve slightly better mediastinal lymph node dissection (N2) in terms of assessing a greater number of mediastinal lymph nodes and nodal stations. This may be attributed to a better visual field during mediastinal nodal clearance by an open approach. Also, nodal upstaging was consistently more common with an open approach. In terms of long-term outcomes, both overall survival and disease-free survival rates were similar between the two groups, with VATS offering a slightly better survival benefit. Irrespective of the increased rates of nodal upstaging by an open approach, we conclude that VATS should be considered a highly efficient alternative to thoracotomy in both early and locally advanced NSCLC.