Intramuscular injection of botulinum toxin A (BTXA) is commonly used for the treatment of forehead wrinkles. In practice, physicians often use an intradermal injection for this purpose, as they feel that there is a lower risk of adverse effects compared with intramuscular injection. However, there are no direct comparative studies between those two injection modalities. We conducted a 24-week long, double-blinded, split-face, pilot study of three participants to compare the efficacy and safety of intradermal or intramuscular injection of BTXA for the treatment of forehead wrinkles. Maximum improvement of wrinkles and the time to achieve maximum effect were similar for both methods. The brow level was lower on the intramuscular injection side throughout the follow-up period for all participants. Subjective satisfaction with wrinkles was similar on both sides, but patients felt more heaviness of the eyebrow on the intramuscular side. No serious side effects were noted. In conclusion, the anti-wrinkle effect of BTXA was not significantly different between intramuscular and intradermal injections. However, side effects such as eyebrow ptosis, and heaviness were more prominent after intramuscular injection.