Micafungin and anidulafungin are two newer antifungal drugs from the echinocandine class. They are used as monotherapy or in combination with azole-antifungal drugs. The optimized clinical treatment course for the echinocandin drugs with regard to the different infection types and patient subgroups (renal or hepatic impairment, overweight) is still under debate. Therefore, an easy and rugged assay for these two drugs is highly desirable. We here present a method for the quantification of micafungin or anidulafungin in human plasma, applying protein precipitation as sample preparation, reversed phase separation of the analytes and UV-detection and simultaneous tandem mass spectrometry. Anidulafungin served as I.S. for micafungin quantification and vice versa. The method was validated in the calibration ranges from 0.1 μg/ml to 20 μg/ml for both substances. Intra-day precision and accuracies recorded with the UV-detector were 1.80% and 2.65% for micafungin and 4.30% and 10.44% for anidulafungin at the 0.1 μg/ml level. The respective data at the 1 μg/ml level were 2.25% and -0.83% for micafungin and 4.35% and -1.85% for anidulafungin and at the 20 μg/ml level 0.97% and -2.98% for micafungin and 1.04% and 4.74% for anidulafungin, respectively. With the mass spectrometer, because of the unique properties of the analyte molecules, no acceptable validation results could be achieved. Therefore, the mass spectrometric chromatograms served only as identity confirmation of the observed UV-peaks.