The chemistry of acetone on the oxidized and reduced surfaces of TiO2(110) was examined using temperature-programmed desorption (TPD) and high-resolution electron energy-loss spectroscopy (HREELS). The reduced surface was prepared with about 7% oxygen vacancy sites by annealing in ultrahigh vacuum (UHV) at 850 K, and the oxidized surface was prepared by exposure of the reduced surface to molecular oxygen at 95 K followed by heating the surface to a variety of temperatures between 200 and 500 K. Acetone adsorbs molecularly on the reduced surface with no evidence for either decomposition or preferential binding at vacancy sites. On the basis of HREELS, the majority of acetone molecules adsorbed in an eta(1) configuration at Ti4+ sites through interaction of lone-pair electrons on the carbonyl oxygen atom. Repulsive acetone-acetone interactions shift the desorption peak from 345 K at low coverage to 175 K as the first layer saturates with a coverage of similar to1 ML. In contrast, about 7% of the acetone adlayer decomposes when the surface is pretreated with molecular oxygen. Acetate is among the detected decomposition products but only comprises about one-third of the amount of decomposed acetone, and its yield depends on the temperature at which the O-2-exposed surface was preheated to prior to acetone adsorption. Aside from the small level of irreversible decomposition, about 0.25 ML of acetone is stabilized to 375 K by coadsorbed oxygen. These acetone species exhibit an HREELS spectrum unlike that of eta(1)-acetone or of any other species proposed to exist from the interaction of acetone with TiO2 powders. On the basis of the presence of extensive O-16/O-18 exchange between acetone and coadsorbed oxygen in the 375 K acetone TPD state, it is proposed that an acetone-oxygen complex forms on the TiO2(110) surface through nucleophilic attack of oxygen on the carbonyl carbon atom of acetone. The reaction between acetone and oxygen is initiated at temperatures as low as 135 K based on HREELS. The major decomposition pathway of the acetone-oxygen complex liberates acetone in the 375 K TPD peak. This species may be a key intermediate in acetone thermal and photolytic chemistry on TiO2 surfaces.