Describe the coronavirus disease of 2019 (COVID-19) vaccine-related headache characteristics. Determine factors associated with developing headaches and factors related to prolonged headaches (≥ 48h) among COVID-19 vaccine receivers. 

Vaccines are the safest tools for preventing COVID-19-related morbidity/mortality. Headaches are among the most reported neurological symptoms after vaccination.

A retrospective, web-based, population-based cross-sectional cohort study between April 2021 - March 2022 at an academic hospital affiliated with Tehran University of Medical Sciences.

Of 1822 individuals (mean age: 34.49 ± 11.09, female: 71.5%), 1822, 1122, and 203 received 1^st, 2^nd, and 3^rd dose. Sinopharm, AstraZeneca, and Sputnik-V were the most injected vaccines. We found a headache prevalence of 21.7% - 36.5% following vaccination. More than half of those with post-vaccination headaches reported a previous history of headaches, of whom nearly 38% - 67% reported similar post-vaccination headaches to primary headaches. More than 65% of patients reported similarities between their headaches following COVID-19 infection and COVID-19 vaccination. Following vaccination, most of the patients reported bilateral pressing headaches with moderate intensity, affecting the entire head or multiple head/neck regions. The median duration of initiating headaches following vaccination was 8.0 – 10.0 hours, with a median attack duration of 2.0 – 3.0 hours. Headaches lasted for a median of 12.0 – 48.0 hours. Although a history of primary headaches and post-COVID-19 headaches increased the odds of post-vaccination headaches, they reduced the odds of prolonged post-vaccination headaches. Compared to inactivated vaccines, vector ones increased the odds of both occurrence and prolonged post-vaccination headache. Other factors associated with increased odds of post-vaccination headaches were headaches following previous vaccine doses and post-vaccination fever. 

The headache prevalence following vaccination was 21.7% - 36.5%. History of primary headache, post-COVID-19 headache, headaches following previous vaccine doses, vector vaccines, and post-vaccine fever increased the odds of post-vaccination headache.