Samples used in electron microscopy are traditionally required to be stable under vacuum. However, many organic compounds with high vapor pressures readily sublime at room temperature, a process that is further accelerated under the high-vacuum conditions of an electron microscope. Here, we demonstrate for the first time the structure determination of vacuum-sensitive organic compounds in their solid state at room temperature using electron crystallography. Serial electron diffraction was employed to obtain sub-Å-resolution structures of anthracene and pyrene, two representative organic molecules which sublimate under the high-vacuum conditions of a transmission electron microscope. This was made possible by a simple sample preparation technique in which ultrathin crystals are encapsulated with a formvar layer to prevent sublimation under vacuum. By combining serial electron diffraction with formvar encapsulation, we demonstrate high-resolution structure determination of vacuum-sensitive samples at room temperature rather than cryogenic conditions. Moreover, by avoiding low-temperature phase transitions that can alter material properties, this method expands the accessible temperature range for studying the structural characteristics of vacuum-sensitive materials.