Background: A simple, sensitive, and rapid extraction method based on high-frequency (H-F) heating was developed for drug analysis in human nails. Methods: A human nail was placed in a glass tube with an extraction solvent (methanol and 0.1% formic acid; 7:3, v/v), and a ferromagnetic alloy (pyrofoil) was wrapped in a spiral around the glass tube. Then, the glass tube was placed in a Curie point pyrolyzer, and a H-F alternating voltage (600 kHz) was applied. The sample and extraction solvent were heated at the Curie temperature for 3 min. Different Curie temperatures were applied by changing the pyrofoil (160 °C, 170 °C, 220 °C, and 255 °C). Results: The caffeine in the nail was effectively and rapidly extracted into the extraction solvent with the pyrofoil at 220 °C. The peak area obtained for the caffeine using liquid chromatography mass spectrometry (LC-MS/MS) was five times that of what was obtained after conventional ultrasonic irradiation extraction. Because the extraction uses high-pressure and high-temperature conditions in a test tube, the drugs that were strongly incorporated in nails could be extracted into the solvent. The amount of caffeine extracted was independent of the size of the pieces in the sample. Conclusions: Therefore, the sensitive determination of target drugs in nails is possible with rapid (20 min, including H-F extraction for 3 min) and simple sample preparation. The developed method was applied to a nail from a patient with hypertension.