A retrospective comparative study was conducted to compare the efficacy of monoclonal antibody drugs against the calcitonin gene-related peptide pathway in migraine and to establish whether they can be considered equivalent therapeutic alternatives for this pathology. A total of 21 patients with chronic migraine were treated with Fremanezumab 225 mg/30 days and 24 patients treated with Erenumab 70 mg/30 days for at least 6 months. Data were collected at baseline and at six months using the following scales: Headache Impact Test (HIT), Migraine Disability Assessment Scale (MIDAS), and a numerical scale of pain intensity (0 (no pain) and 10 (unbearable pain)). Days of migraine per month were recorded. Mean HIT at baseline and 6 months for Fremanezumab and Erenumab was 68.6 (62–76) and 54 (36–70) and 66 (42–78) and 53 (9–72), respectively. In both cases, it decreased by more than 6 points (efficacy criteria). Mean MIDAS at baseline and 6 months for Fremanezumab and Erenumab was 70 (25–127) and 25 (0–135) and 73.3 (19–150) and 23 (0–68), respectively. In both cases, it decreased by more than 30% (efficacy criteria). Mean pain intensity at baseline and 6 months for Fremanezumab and Erenumab was 8.8 (6–10) and 6(5–8) and 8.6 (7–10) and 6 (10–0), respectively. Mean number of migraine days in a month at baseline and 6 months for Fremanezumab and Erenumab were 16.6 (10–30) and 5.3 (0–11) days and 17 (3–30) and 5.8(–15) days, respectively. In both cases, the reduction was > 50%. It can be concluded that the initial values of the scales are very similar. The initial situation of the patient is not a trigger for the use of one drug or the other. Clinically, there is no difference between the two drugs.