The relationship between the spreading of antifoam oils and their performance is much discussed in the literature, but a demonstrated connection between antifoam spreading and performance has been lacking. This paper reports the performance of a poly(dimethylsiloxane) (PDMS)-based antifoam on foam produced by 12 surfactant solutions. These include single or mixed surfactant systems, including impure surfactant mixtures to model fabric washing detergents. The oil film spreading pressure, πo/w, is presented as a simple and relevant measurement of the thermodynamics of antifoam oil spreading. Antifoaming efficacy was measured as the relative reduction in the initial foam height, ∆Hrel, using cylinder shake tests at a fixed antifoam dosage. ∆Hrel is shown to increase with πo/w, demonstrating a strong statistical correlation between antifoam oil spreading and its performance. Antifoam effectiveness varies with surfactant concentration, surfactant type, and surfactant hydrophobe size and also with increased density of surfactant packing. Surface shear viscosity, µ s , was used to quantify surfactant packing. Antifoam effectiveness decreases with increasing surface shear viscosity. This finding provides a potentially useful link between antifoam efficacy and surfactant selection based on well-established surfactant molecular packing parameters. The role of spreading of antifoam oil at the air/surfactant solution interface is investigated. Oil film spreading pressure is shown to decrease by a power law function with increasing surface shear viscosity of the surfactant film. A new fluorescence technique was used to measure the extent of PDMS spreading. Initial results suggest a correlation between the spreading distance and antifoaming performance. An antifoam mechanism is proposed that features antifoam spreading as a direct contributor to bubble film rupture and incorporates surfactant type and concentration, surfactant packing density, and antifoam oil film spreading pressure as factors contributing to antifoam efficacy.