Intermetallic phase formation due to diffusion reactions between nickel and titanium in a fast dynamic system, such as the thermal spray coating process is reported here for the first time. In the present work, we examined the possibility of the ultra-fast (in the order of microseconds) reaction of nickel single molten droplets deposited by plasma spray on a titanium substrate and the role of this interfacial reaction on the droplet spreading process. The splat morphology and splat-substrate interfaces were characterised using FIB and TEM. Titanium was found to diffuse into the nickel splat, but not vice versa. Excellent splat-substrate contact was observed with the co-existence of three interfacial layers of TiNi3, TiNi, and Ti2Ni having a total thickness from 0.4 to 1μm. In contrast, poor contact and delamination was observed at the splat periphery without the formation of interfacial layers. This indicated that the microsecond chemical reactions occurring between the nickel droplet and titanium substrate can enhance the interface bonding. We also found that the diffusion reaction to form intermetallics occurred after the splat solidified, thus it seems unlikely to influence the spreading of the splat on the solid surface.