Fast pyrolysis bio-oil oil is a promising alternative to fossil fuels and is currently entering the heating oil market. However, there is a lack of available information about the phase stability of bio-oil. The water-soluble and water-insoluble compounds in bio-oil can either be in one homogeneous phase or form two individual phases, to which we refer to as phase separation. Phase separation can occur immediately after condensation of the pyrolysis vapors to bio-oil because of certain pyrolysis conditions or type of raw material or after years of aging because of changes in composition caused by repolymerization reactions. We present how the phase separation of bio-oils is related to the chemical composition and show that the probability of phase separation can be predicted with a numerical stability index based on the chemical composition. The chemical composition of the bio-oils studied was characterized using a solvent extraction scheme that describes the composition of bio-oil as a blend of three macro fractions: C-1-C-6 oxygenated molecules (named co-solvents), water-insoluble molecules, and water-soluble polar molecules (including water but excluding the co-solvents), e.g., anhydrosugars. The results show that the required amount of co-solvent to dissolve both fractions and keep the bio-oil homogeneous varies depending upon the chemical composition. The minimum amount of co-solvent for homogeneous bio-oils was observed to be from 15 to 30 wt %. The correlation between the chemical composition and homogeneity of fresh and aged bio-oils is shown in ternary-phase diagrams. Addition experiments were made with model compounds to cover a larger part of the phase diagram.