Equisetumone (1), an unprecedented sesquiterpenoid, which possesses a novel 4,5-olide tricyclic trans-caryophyllane skeleton, was isolated from the Equisetum palustre fern. The structure of 1 was established by extensive spectral data analysis. This usual metabolite was probably derived from the caryophyllane class of sesquiterpenes, and a biosynthetic pathway was proposed.