3′-(N-Phthalimido)glutarimide, commonly known as thalidomide (TD), is one of the most famous chiral drugs, because of its tragic history. Although the R-enantiomers of TD have positive medical effects, the S-enantiomers have dangerous side effects, and consequently, the enantiomeric purity of TD in a solid state and the chiral inversion of TD in physiological conditions have attracted considerable attention and prompted discussion on the "TD paradox". Subsequently, the physicochemical properties of TD in the solid state have been indicated to be as essential as those in the solution state for understanding the pharmacodynamics and pharmacokinetics of TD. Herein, we demonstrate that the sublimation method is beneficial in the crystal growth of TD compared with solvent−evaporation methods. Structural and optical analyses demonstrated that sublimination produced very thin, transparent, and defect-free single crystals with high crystal-surface parallelism; chromatographic analysis suggested that a chiral inversion of TD molecules occurs during the sublimation even beneath the melting point under ambient humidity. The potential occurrence of chiral inversion of TD in the gas phase with atmospheric water vapor is a crucial finding in the use of sublimation in purifying chiral drugs to avoid adverse drug-induced outcomes. The crystal growth and potential chiral inversion of TD by sublimation should contribute to providing important information for pharmaceutical sciences and industry.