Introduction: Photodynamic therapy is a proven therapeutic modality in the management of variety of pathologies involving the human body. Our aim in this clinical study is to prospectively evaluate the outcome following interstitial photodynamic therapy for patients with vascular anomalies. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. Materials and methods: Forty-three patients were referred to the UCLH Head and Neck Centre for treatment of vascular anomalies of the head and neck, including: infantile and congenital haemangiomas, venous, lymphatic and arteriovenous malformations. After multidisciplinary discussion, all patients underwent interstitial photodynamic therapy under general anaesthesia, using 0.15 mg/ kg mTHPC as the photosensitising agent. Following treatment, patients were followed-up for a mean of 21 months. Results: Fifteen out of nineteen patients who presented with long-term pain reported improvement after treatment. Also, 7/8 reported significant reduction of bleeding related to their vascular anomaly. Improvement of swelling was reported by 28/35 patients; while reduction of infection episodes was evident in 8/11 patients and 31/36 reported reduction in the disfigurement caused by their pathology. Significant reduction of swallowing problems was reported in 9/12 patients, and breathing problems in 7/9 patients. Clinical assessment showed that half of the patients had 'good response' to the treatment. Moderate clinical response was reported by 13 (30.2%) patients. Radiological assessment comparing imaging 6-week post-PDT to the baseline showed moderate response in 11 (25.6%) patients and significant response in 15 (34.9%) patients. Conclusion: This study on 43 patients with vascular anomalies undergoing interstitial photodynamic therapy provided evidence that PDT is a successful modality in the management of these pathologies that are resistant to conventional modalities, with minimal side effects.