Abstract Background Talimogene Laherparepvec (TVEC), a genetically modified GM-CSF expressing HSV1 Virus that preferentially replicates in tumor cells is approved in Europe for use in melanoma patients with injectable metastatic lesions in stage III-IVM1a. Approval was based on the OPTIM study which did also include patients with distant metastases and demonstrated a ORR of 40.5% and a CR rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with TVEC in a real life clinical setting outside of clinical studies. Methods To this aim a retrospective chart review in 7 melanoma centers in Austria and 1 center in Switzerland was conducted and anonymized data on disease stage, treatment duration, treatment response by investigator assessment following RECIST 1.1, tolerability as well as data on follow up therapies was collected. Results A total of 62 patients received TVEC since December of 2016. The majority of patients were AJCC stage IIIB and IIIC. Two patients with stage IV M1b and M1d who had complete control of their distant metastases and a locoregional progression were treated in parallel with a PD-1 antibody in one case and in parallel with a BRAF/MEK inhibitor combination in the other. In 3 other cases TVEC was used in combination with a PD-1 inhibitor as first-line of therapy. The median number of intralesional injection cycles was 11. The ORR was 67,7%; 50% of patients achieved a complete remission. 7 of 31 patients with a CR had a subsequent progression, 4 with distant and 3 with locoregional metastases. The main side effects observed were fever and chills. Conclusions In this real life cohort treatment of TVEC shows a high overall and complete remission rate with the majority of complete responses being durable. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure C. Hoeller: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. J.M. Ressler: Speaker Bureau / Expert testimony: Amgen. H. Kehrer: Advisory / Consultancy: Amgen. P. Koelblinger: Advisory / Consultancy: Amgen. F. Weihsengruber: Advisory / Consultancy: Amgen. J. Kofler: Advisory / Consultancy: Amgen. E. Richtig: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. O.A. Michielin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. C. Hafner: Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.