Trichocereus macrogonus is one of a number of similar species that may be called San Pedro cactus.

The species has erect stems, 2.5–5 m (8–16 ft) tall, with branches generally with a diameter of 6–15 cm (2–6 in), occasionally more.

The circular areoles are 6 mm (0.2 in) across, grey or dark brown, with needle-like spines, and are spaced more than 2.5 cm (1.0 in) apart.

macrogonus, older areoles may have up to 20, with three or four prominent, longer and more robust central spines up to 5 cm (2.0 in) long.

[6] The specific epithet macrogonus is derived from the Greek words makros for 'large' and gonia for 'edge' and refers to the ribs of the species.

[8] As of 2023[update], Plants of the World Online accepted two varieties:[2] Plants of the World Online regards the species as native to Peru, Ecuador, and Bolivia, and introduced to central Chile, Colombia, mainland Spain and the Canary Islands.

[10] Ritual uses of the species are depicted on pre-Columbian Peruvian ceramics and other archaeological objects, with one use dated to about 1300 BCE.

Reported concentrations of mescaline vary widely, with causes suggested to include: taxonomic uncertainty leading to difficulties in identification; genetic differences between species and within populations; environmental factors, such as temperature and water availability, affecting plants during growth; and variations in laboratory techniques.

[12] Some studies have reported no mescaline content in wild-harvested Peruvian specimens of T. macrogonus,[13] and in plants grown in Europe.

pachanoi), the lowest found was 0.4% of dry weight compared to 4.7% for a form on sale in traditional Peruvian shamans' markets.