Emulsification of intravitreal silicone oil has been observed as a late complication after its use as a retinal tamponade. We compared the emulsification potential of silicone oil of different viscosities (100 centistokes [cs], 1000 cs, and 12,500 cs) and molecular composition in an in vitro model using a commercial detergent (benzalkonium chloride) and physiologic surface-active agents (human serum and lysed red blood cells). We found that silicone oils that have low-molecular-weight contents emulsify more readily than those that do not. Moreover, the extent and susceptibility to emulsification increases with decreasing viscosity or with an increase in the proportion of low-molecular-weight constituents. Hence, higher-molecular-weight (viscosity) oils or removal of low-molecular-weight components from medical grade fluid may lessen the emulsification observed clinically.