A near-infrared (NIR) fiber-optic probe was used at-line to study the blending dynamics of pharmaceutical powder blends on a mass-balanced basis. The probe with a flexible fiber-optic cable can be inserted directly into a 10-L bin blender to get quantitative readings. NIR calibration models were developed and validated for the probe based on a designed 50-sample calibration set. A model formulation containing acetaminophen, mannitol, Avicel, magnesium stearate and AcDiSol was used in the study. The blending study was conducted at 18 rpm for 20 min. NIR probe scans were performed at 1 min intervals and five different locations in the bin. Thief samples were collected and later analyzed by a bench-top NIR instrument to confirm the results from the probe. Complete blending profiles were constructed and compared based on the assay results from both instruments.