Oncological and functional outcome of transoral laser microsurgery (TLM) for primary treatment of oropharyngeal cancer was examined using a multimodal treatment concept. A total of 368 patients with oropharyngeal squamous cell carcinoma (pT1-4, pN0-2, M0) underwent TLM +/- neck dissection (85%), +/- (chemo)radiotherapy (57%). The majority of patients had advanced stage III and IVa disease (79%). Five-year Kaplan-Meier estimates for local control were 83.5% for pT1, 74.1% for pT2, 77.3% for pT3, and 76.0% for pT4a tumors. Five-year estimates of overall, disease-specific, and recurrence-free survival for stage I were 76.0%, 92.8%, and 69.1%; for stage II 71.1%, 85.7%, and 49.6%; for stage III 61.7%, 72.5%, and 58.8%; and for stage IVa 57.3%, 73.7%, and 63.9%, respectively. Postoperative (chemo)radiotherapy improved the outcome for advanced disease. p16-positive tumors had superior survival estimates. Overall, 93.5% maintained regular oral nutrition without feeding tube dependency. Primary TLM in multimodal concepts of treatment offers good oncologic outcome even for advanced-stage oropharyngeal cancer.