In this prospective study we have evaluated the predictive role of intratumoral microvessel density (MVD) for the therapeutic response and progression of inoperable oropharyngeal cancer (OPCC) treated with radiotherapy. Thirty-five OPCC patients were enrolled in this study. Biopsies from the primary tumor were taken before and after 20 Gy irradiation. Pathological factors such as histological grade, mitotic activity index and MVD were determined in both samples. Correlations of these factors with response to therapy, progression-free and overall survival were analyzed after a follow-up period of a minimum of 50 months. Objective response and survival was independent of the pretreatment MVD of OPCC. On the other hand, objective response was significantly affected by stage and low posttreatment MVD. Response to irradiation, and therapy-induced low postirradiation MVD were significant indicators of better overall and progression-free survival. We have shown in this small exploratory study that the anti-angiogenic effect of irradiation has a predictive value of the success of radiotherapy in locally advanced OPCC and can be used to select a radioresistant patient population which might require a more aggressive protocol.