In principle, cis–trans notation should not be used for alkenes with two or more different substituents. Instead the E–Z notation is used based on the priority of the substituents using the Cahn–Ingold–Prelog (CIP) priority rules for absolute configuration. The IUPAC standard designations E and Z are unambiguous in all cases, and therefore are especially useful for tri- and tetrasubstituted alkenes to avoid any confusion about which groups are being identified as cis or trans to each other.
Z (from the German ) means "together". E (from the German ) means "opposed" in the sense of "opposite". That is, Z has the higher-priority groups cis to each other and E has the higher-priority groups trans to each other. Whether a molecular configuration is designated E or Z is determined by the CIP rules; higher atomic numbers are given higher priority. For each of the two atoms in the double bond, it is necessary to determine the priority of each substituent. If both the higher-priority substituents are on the same side, the arrangement is Z; if on opposite sides, the arrangement is E.
Because the cis–trans and E–Z systems compare different groups on the alkene, it is not strictly true that Z corresponds to cis and E corresponds to trans. For example, trans-2-chlorobut-2-ene (the two methyl groups, C1 and C4, on the but-2-ene backbone are trans to each other) is (Z)-2-chlorobut-2-ene (the chlorine and C4 are together because C1 and C4 are opposite).