In Tibetan Buddhism, Om is often placed at the beginning of mantras and dharanis. Probably the most well known mantra is "Om mani padme hum", the six syllable mantra of the Bodhisattva of compassion, Avalokiteśvara. This mantra is particularly associated with the four-armed Shadakshari form of Avalokiteśvara. Moreover, as a seed syllable (bija mantra), Aum is considered sacred and holy in Esoteric Buddhism.

Some scholars interpret the first word of the mantra oṃ maṇipadme hūṃ to be auṃ, with a meaning similar to Hinduism - the totality of sound, existence and consciousness.

Oṃ has been described by the 14th Dalai Lama as "composed of three pure letters, A, U, and M. These symbolize the impure body, speech, and mind of everyday unenlightened life of a practitioner; they also symbolize the pure exalted body, speech and mind of an enlightened Buddha." According to Simpkins, Om is a part of many mantras in Tibetan Buddhism and is a symbolism for "wholeness, perfection and the infinite"