[6][7] After one year of service, he returned to pursue his studies of mathematics at the University of Lyon and finally obtained his degree Licencié ès Sciences Mathématiques in 1894.

After working with stereochemistry and énines, Grignard was not impressed with the subject matter and asked Barbier about a new direction for his doctoral research.

[10] Barbier advised that Grignard study how a failed Saytzeff reaction using zinc, was successful, in low yields, after substitution of magnesium.

[10] Grignard hypothesized that the aldehyde or ketone prevented the magnesium from reacting with the alkyl halide, accounting for the low yields.

Named after him, this organo-magnesium compound (R-MgX) (R = alkyl ; X = Halogen) readily reacts with ketones, aldehydes, and alkenes to produce their respective alcohols in impressive yields.

In 1901, he published his doctoral thesis titled "Thèses sur les combinaisons organomagnesiennes mixtes et leur application à des synthèses d‘acides, d‘alcools et d‘hydrocarbures".

[13][14] During World War I he studied chemical warfare agents with Georges Urbain at Sorbonne University, particularly the manufacture of phosgene and the detection of mustard gas.

[18] Grignard is most noted for devising a new method for generating carbon-carbon bonds using magnesium to couple ketones and alkyl halides.