Background: Migraine is a common and disabling primary headache disorder, associated with many medical comorbidities, highly prevalent, with complex treatment and management. Currently, monoclonal antibodies targeting the trigeminal sensory neuropeptide, calcitonin gene-related peptide (CGRP), are available. The aim of this protocol is to provide a review comparing the effects and safety profile of different monoclonal antibodies in migraine patients. Methods: The literature search will be performed through the MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), Web of Science and Scopus databases, following the PICO strategy. Real World studies and randomized clinical trials assessing the effect of monoclonal antibodies against CGRP interventions (erenumab, eptinezumab, fremanezumab and galcanezumab) on monthly migraine days (MMD), monthly headache days (MHD), headache impact test (HIT-6) and triptan days of use (TriD) will be included. In Real World studies, the DerSimonian and Laird method will be used to calculate pooled estimates of the mean change difference and in randomized clinical trials, a network meta-analysis will be performed to estimate the comparative effects of different monoclonal antibodies against CGRP. Results: The findings of this study will be reported in a peer-reviewed journal. Conclusions: This study will provide evidence to health professionals on the efficacy and safety of different monoclonal antibodies against CGRP on the outcomes studied.