Isotretinoin compositions having improved bioavailability are disclosed. The compositions are oral formulations containing isotretinoin, a lipid excipient and a cosolvent, wherein the ratio of isotretinoin to the lipid excipient is from about 1:1.2 to about 1:1.6. The compositions can be in the form of a pharmaceutically acceptable oral dosage form such as a capsule or compressed tablet wherein the isotretinoin is adsorbed onto blended particles of a cellulosic polymer and silicon dioxide in combination with a lipid excipient such as soy phosphatidylcholine and a cosolvent such as propylene glycol. Methods of preparing the compositions and methods of treatment using the compositions are also disclosed.