Background: Quality of life (QoL) has become increasingly important in cancer treatment. It refers to the patient’s perception of the effects of the disease and therapy, and their impact on daily functioning and general feeling of well being. Material and Methods: In this prospective study, a total of 100 patients treated at our institution, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific EORTC QLQ-H&N35 module. The questionnaires were distributed to the patients between 12 and 60 months postoperatively. Results: Global QoL score was 58.3 and mean score for functioning scale was 76.7. Fatigue (28.7 ± 26.1), followed by financial problems (27.7 ± 33.5), insomnia (26.7 ± 34.5) and pain (26.3 ± 29.9) had highest symptom score on QLQ-C30. Fatigue (r=-0.488), insomnia (r=-0.416) and pain (r =-0.448) showed highest value for significantly negative correlation to global QoL. In the H&N35 module, restriction of mouth opening (43.3 ± 38.6), dry mouth (40.7 ± 36.9), sticky saliva (37.3 ± 37.1) and eating in public (33.8 ± 31.9) were the four worst symptoms. Swallowing problem (r=-0.438), eating in public (r=-0.420) and persistent severe speech (r=-0.398) ranked as the three worst symptoms with highest value for significantly negative correlation to global QoL. Conclusions: Longterm QoL after oncologic surgery and microvascular free flap reconstruction in patients with oral cancer is satisfactory. Measuring QoL should be considered as part of the evaluation of cancer treatment.