Blowfish's use of a 64-bit block size (as opposed to e.g. AES's 128-bit block size) makes it vulnerable to birthday attacks, particularly in contexts like HTTPS. In 2016, the SWEET32 attack demonstrated how to leverage birthday attacks to perform plaintext recovery (i.e. decrypting ciphertext) against ciphers with a 64-bit block size. The GnuPG project recommends that Blowfish not be used to encrypt files larger than 4 GB due to its small block size.

A reduced-round variant of Blowfish is known to be susceptible to known-plaintext attacks on reflectively weak keys. Blowfish implementations use 16 rounds of encryption, and are not susceptible to this attack. Nevertheless, Bruce Schneier has recommended migrating to his Blowfish successor, Twofish.