Immunization offers the most effective protection. Currently, there are 4 widely used vaccines of assured quality: FSME-Immun and Encepur, manufactured in Austria and Germany respectively, and based on European strains of the virus; and TBE-Moscow and EnceVir, manufactured in the Russian Federation and based on Far-Eastern strains. The 4 vaccines are considered to be safe and effective.

In areas where the disease is highly endemic, WHO recommends that vaccination be offered to all age groups, including children.

Ticks also transmit Borreliosis (Lyme disease), which is a bacterial infection. TBE vaccination is not effective against this disease, which however is treatable with antimicrobials.