Thiamethoxam is the ISO common name for a mixture of cis-trans isomers used as a systemic insecticide of the neonicotinoid class. It has a broad spectrum of activity against many types of insects and can be used as a seed dressing.

A 2018 review by the European Food Safety Authority (EFSA) concluded that most uses of neonicotinoid pesticides such as Thiamethoxam represent a risk to wild bees and honeybees. In 2022 the United States Environmental Protection Agency (EPA) concluded that Thiamethoxam is likely to adversely affect 77 percent of federally listed endangered or threatened species and 81 percent of critical habitats. The pesticide has been banned for all outdoor use in the entire European Union since 2018, but has a partial approval in the U.S. and other parts of the world, where it is widely used.

Thiamethoxam was developed by Ciba-Geigy (now Syngenta) in 1991 and launched in 1998; a patent dispute arose with Bayer which already had patents covering other neonicotinoids including imidacloprid and clothianidin. In 2002 the dispute was settled, with Syngenta paying Bayer $120 million in exchange for worldwide rights to thiamethoxam.

Thiamethoxam was first prepared by chemists at Ciba Geigy in 1991. S-Methyl-N-nitro-isothiourea is treated with methylamine to give N-methyl nitroguanidine. This intermediate is used in a Mannich reaction with formaldehyde in formic acid to give 3-methyl-4-nitroimino-1,3,5-oxadiazinane. In the final step, the heterocycle is N-alkylated with a thiazole derivative to give a mixture of E and Z isomers of the final product.

Thiamethoxam is a broad-spectrum, systemic insecticide, which means it is absorbed quickly by plants and transported to all of its parts, including pollen, where it acts to deter insect feeding.^{[citation needed]} An insect can absorb it in its stomach after feeding, or through direct contact, including through its tracheal system. The compound gets in the way of information transfer between nerve cells by interfering with nicotinic acetylcholine receptors in the central nervous system, and eventually paralyzes the muscles of the insects.

Syngenta asserts that thiamethoxam improves plant vigor by triggering physiological reactions within the plant, which induce the expression of specific "functional proteins" involved in various stress defense mechanisms of the plant allowing it to better cope under tough growing conditions, such as "drought and heat stress leading to protein degradation, low pH, high soil salinity, free radicals from UV radiation, toxic levels of aluminum, wounding from pests, wind, hail, etc, virus attack".

The selective toxicity of neonicotinoids like thiamethoxam for insects versus mammals is due to the higher sensitivity of insects' acetylcholine receptors. The Food and Agriculture Organization (FAO) of the U.N. assessed thiamethoxam as "moderately hazardous to humans (WHO class III)", because it is harmful if swallowed. It found it to be no skin or eye irritant, and not mutagenic in any in vitro and in vivo toxicology tests.

FAO described thiamethoxam as non-toxic to fish, daphnia and algae, mildly toxic for birds, highly toxic to midges and acutely toxic for bees. The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification is: "Harmful if swallowed. Very toxic to aquatic life with long lasting effects". Thiamethoxam at sublethal concentrations can increase aggressiveness and cannibalism in commercially harvested shrimp such as Procambarus clarkii In bioassays of aquatic organisms, fish, aquatic primary producers, mollusks, worms, and rotifers are often largely insensitive to thiamethoxam concentrations found in surface waters, but insects, such as chironomid larvae are especially susceptible.