The aim of this study was to fabricate novel poly(lactic-co-glycolic acid) microspheres (PLGA MSs) containing triamcinolone acetonide (TA), a potent corticosteroid, to achieve the sustained release profile in joints after intra-articular injection. The TA-loaded MSs were prepared by layering the suspended drug crystals with PLGA using spray-drying. The MS consisting of the drug crystals, PLGA, and lecithin was spherical with size 9.7-10.3 μm. Hyperspectral analysis (CytoViva ® ) and powder X-ray diffraction studies revealed that the drug crystals were predominantly located in the inner compartment of MS in a stable crystalline form. In an in vitro release test under sink condition, over 90% of TA was released from drug powder within 1 h. However, the MS system released only 35% of the drug during 1 h, achieving 80% drug release after 48 h. Moreover, the steroid-embedded MS was stable for 6 months under long-term storage condition (25 C/60% RH) with no physicochemical changes. These findings suggest that PLGAbased MSs of TA can be a sustained release formula for the treatment of chronic diseases with less frequent intra-articular injection and improved patient compliance.