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Background and Importance Chronic migraine (CM) is a highly disabling neurological disorder with limited preventive options. Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has demonstrated effectiveness in CM prevention. Botulinum toxin (BTX) is an established preventive treatment for CM, but evidence regarding the combined use of BTX and atogepant remains limited.Aim and Objectives To compare the effectiveness of botulinum toxin plus atogepant (BTX-ATO) versus atogepant monotherapy (ATOm) in patients with CM.Material and Methods Observational, retrospective, multicentre study conducted in two tertiary hospitals in patients with CM treated with atogepant for at least 3 months. The cohorts compared were patients treated with BTX-ATO versus ATOm. The main variable was the difference in the change in mean monthly migraine days (MMD) at 3 months compared with baseline between the two cohorts. Secondary variables included the proportion of patients achieving ≥50% reduction in MMD at 3 months (MMD ≥50%), as well as 30–49% and 0–29% reductions, between cohorts.Demographic, clinical, and treatment data were obtained from the Electronic Health Record (Selene) and the electronic prescribing programme (Farmatools). Statistical analysis included descriptive measures, the Mann–Whitney U test and the Chi-squared test to compare differences, using Python (3.12.7) for data processing and analysis.Results A total of 45 patients were included, 91.11% (41/45) were women with a mean age of 47.42 years(SD = 11.0). The BTX-ATO cohort included 29 patients (64.4%) and the ATOm cohort 16 patients (35.6%), with baseline MMD of 20 and 21 days, respectively. After 3 months, MMD decreased to 13 days in the BTX-ATO cohort and 14 days in the ATOm cohort, with an absolute difference of 1 day between cohorts (p = 0.329). The proportion of patients achieving MMD≥50% was 41.4% (12/29) with BTX-ATO and 25.0% (4/16) with ATOm. MMD 30–49% was achieved by 6.9% (2/29) with BTX-ATO and 12.5% (2/16) with ATOm, while MMD 0–29% was 51.7% (15/29) and 62.5% (10/16), respectively. No statistically significant differences were found in secondary variables (p = 0.507).Conclusion and Relevance Results suggest that the effectiveness of atogepant in chronic migraine, in terms of reducing monthly migraine days, is comparable between patients receiving combination therapy with botulinum toxin and those receiving atogepant monotherapy. Further prospective studies are needed to determine the potential added value of combination therapy.Conflict of Interest No conflict of interest