Background: Intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) and moderate hypofractionation offers an opportunity for defining individual doses and a reduction in overall treatment time in locally advanced head and neck cancer (HNSCC). We present retrospective data on toxicity and locoregional control of a patient cohort treated with an IMRT-SIB concept in comparison to normo-fractionated 3D-conformal radiotherapy (3D-RT). Patients and Methods: Between 2012 and 2014, 67 patients with HNSCC (stages III-IVB) were treated with IMRT-SIB either definitively or in the postoperative setting. These patients were matched with those of patients treated with normo-fractionated 3D-RT before mid-2012 and their clinical courses were compared. Chemotherapy or cetuximab was given concomitantly in both groups in the definitive situation (postoperatively, dependent on risk factors). Results: Significantly less toxicity was found in favor of IMRT-SIB concerning dysphagia, dermatitis, xerostomia, fibrosis, and lymphedema. After a median follow-up of 31 months (range=2-104 months), 3-year locoregional control was 73% for those treated with IMRT-SIB versus 78% for those treated with 3D-RT. Conclusion: This moderately hypofractionated IMRT-SIB concept was shown to be feasible, incurring less toxicity than conventional 3D-RT.