Reducing the particle size of drug materials down to submicron is an important matter in pharmaceutical industry. Cryogenic milling technology is one of the mechanical milling processes, which is mostly utilized in refining grain size of metal and ceramics at extremely low temperature environment. This technique has not been readily studied in application to medical and biotechnology. This paper, therefore, describes the application of cryogenic milling process to reduce particle size of Ibuprofen. The shape and size of the Ibuprofen particle before and after the cryogenic ball milling process were analyzed. XRD analysis was performed to examine a change in crystallinity of Ibuprofen by the cryogenic ball milling process. The results showed that the size of Ibuprofen particles was reduced to 1/10 or less of its initial size. The results also showed that the degree of crystallinity of Ibuprofen was slightly reduced after cryogenic ball milling with nitrogen.