Objectives <p>To compare the results of upfront surgery and non-surgical therapies in resectable advanced oral squamous cell carcinoma.</p> Methods <p>We analyzed a hospital-based database from the state of São Paulo, Brazil. This database contains information on demographic, clinical, pathologic, treatment and outcomes of patients treated for cancer. We compared patients treated by upfront surgery and non-surgical approaches regarding the factors that impact treatment choice and oncologic outcomes. To minimize differences between the groups, we performed two subsets analysis based on cT stage and matched patients in a 1:1 ratio using propensity scores.</p> Results <p>We analyzed 14,585 patients, with 6,421 receiving surgery as part of treatment. Age, gender and cT and cN stage were unevenly distributed in the different treatment modalities. At last notice, 9,091 were dead from disease progression and 2,629 from other causes. Multivariate Cox model disclosed age, cT and cN stage and treatment modality as significant for disease-specific and overall survival. In the subset of patients with cT3 and cT4a primary tumors, we matched patients according to treatment received and surgically treated patients had improved survival outcomes compared to chemoradiation.</p> Conclusion <p>Surgery should be employed as first treatment option in patients with oral squamous cell carcinoma followed by adjuvant treatment when indicated.</p>