Migraine preventive treatment with the CGRP-receptor monoclonal antibody Erenumab can positively impact health-related quality of life (HRQoL) and disease-associated disability. Patient-reported outcome measures (PROMs) are a valuable additional datapoint to real-world evidence covering how treatment affects physical, mental, and social domains of patients’ lives. In this real-world, single-center retrospective observational cohort study, we analyzed clinical performance indicators and PROMs for migraine patients who failed at least four other preventive medications and received Erenumab over the course of one year. Endpoints were the average monthly migraine days as well as PROMs including the MIDAS, EQ-5D-VAS and PROMIS-29. Data were collected digitally via the software heartbeat ONE in an ambulatory care setting as part of the clinical routine. A total of 145 patients treated with Erenumab provided data for 12 months. After 12 months, the median number of monthly migraine days decreased from 9 to 7 days. A clinically relevant reduction in migraine days by ≥30% was reported by 40% of the patients. The migraine-specific MIDAS score, the EQ-5D-VAS measuring the overall health status and all PROMIS domains, except sleep disturbance, changed significantly, reflecting a positive disease progression. This study highlights how patients with a treatment-resistant migraine in an outpatient setting benefit from a preventive treatment with Erenumab. A decrease in migraine days and an increase in HRQoL was maintained over one year. It also underscores the significance of collecting real-world evidence, including PROMs, as an integral component of the healthcare cycle, as such data can reveal additional factors relevant to treatment.