The thermal chemistry of neopentyl iodide on Ni(100) single-crystal surfaces was characterized under vacuum by using temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). The first decomposition step, which takes place around 150 K, is the scission of the C-I bond, the same as in other chemisorbed alkyl halides. Owing to the absence of beta hydrogens, however, no easy decomposition pathway is available for the resulting neopentyl surface species. Neopentane is produced via neopentyl reductive elimination with surface hydrogen, and desorbs in two stages around 140 and 180 K. The yield for this pathway is approximately 45% of the initial neopentyl iodide at saturation (which is approximately 0.2 ML) on the clean nickel, but reaches a value close to 100% if enough hydrogen (or deuterium) is predosed on the surface. The other major carbon-containing product from neopentyl iodide activation is isobutene, which desorbs around 400 K. Isotope labeling experiments demonstrated that the C-C bond that breaks in that reaction is the one between the alpha and beta carbons, and highlighted the fact that the kinetics of the overall reaction displays strong isotope effects upon deuterium substitution at either the alpha or gamma positions. In addition, the hydrogen TPD traces indicated that one of the two hydrogens from the a carbon of the neopentyl group is removed at low temperatures (below 300 K), suggesting that the precursor to isobutene formation is a neopentylidene intermediate.