We showed a relationship among the growth rate, defect generation process, and stability of the metastable phase form II crystal of acetaminophen. Appropriate control of the form II crystal growth rate via slow cooling and nanosize crystal seeding not only suppressed the defect formation but improved the crystallinity of form II. The boundary condition between the interfacial control and transport control was determined based on the relationship between the crystal growth rate and supersaturation. The nanosize crystal seeds met the conditions of interfacial control; thus, the serious defects were suppressed. Finally, better temporal stability of the form II crystal was achieved.