Аннотация:Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce therisk of developing Coronavirus Disease 2019 (COVID-19). Despite the signifcant benefts in terms of reduced risk ofhospitalization and death, diferent adverse events may present after vaccination: among them, headache is one ofthe most common, but nowadays there is no summary presentation of its incidence and no description of its mainfeatures.Methods: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021,looking for record in English and with an abstract and using three main search terms (with specifc variations): COVID19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjectsdeveloping headache after injection, and such information had to be derived from a structured form (i.e. no freereporting). Pooled estimates and 95% confdence intervals were calculated. Analyses were carried out by vaccine vs.placebo, by frst vs. second dose, and by mRNA-based vs. “traditional” vaccines; fnally, we addressed the impact of ageand gender on post-vaccine headache onset.Results: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94%of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in22% (95% CI 18–27%) of subjects after the frst dose of vaccine and in 29% (95% CI 23–35%) after the second, withan extreme heterogeneity. Those receiving placebo reported headache in 10–12% of cases. No diferences weredetected across diferent vaccines or by mRNA-based vs. “traditional” ones. None of the studies reported informationon headache features. A lower prevalence of headache after the frst injection of BNT162b2 among older participantswas shown.Conclusions: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 daysfrom injection, and the lack of diference between vaccine types enable to hypothesize that headache is secondary tosystemic immunological reaction than to a vaccine-type specifc reaction. Some descriptions report onset within thefrst 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phonoand photophobia; in 40–60% of the cases aggravation with activity is observed. The majority of patients used somemedication to treat headache, the one perceived as the most efective being acetylsalicylic acid.Keywords: SARS-CoV-2, COVID-19, Vaccination, Headache, BNT162b2, ChAdOx1, Headache, Adverse Event