: Extraction and determination of naproxen from human plasma were performed using Vortex-Assisted Inverted Dispersive Liquid–Liquid MicroExtraction (VA−IDLLME) and High Performance Liquid Chromatography (HPLC). The parameters affecting extraction recovery such as type and volume of extraction and disperser solvents, pH of sample solution, stirring rate, extraction time and salt addition were optimized. Optimal extraction conditions were: 100 µL dodecane as extraction solvent, 350 µL methanol as disperser solvent, pH of sample = 5, stirring rate: 500 rpm, with no effect of extraction time and no addition of NaCl to the sample solution. Under the optimal conditions a linear range of 1.0–1000.0 ng/mL (R2 = 0.9993) was obtained. Limit of detection, the extraction recovery and preconcentration factor were 0.32 ng/mL, 87% and 108 respectively
