Posaconazole (POS) and caspofungin (CAS) are new therapeutic options for treating fungal infection. This study establishes the activity of POS and CAS against yeast causing invasive fungal infections. In addition, the utility of the E-test system for estimating the minimum inhibitory concentrations (MICs) related to these antifungal drugs has been assessed. The study includes 53 yeast isolates causing invasive fungal infection. MIC50 and MIC90 values were determined by the M27-A2 reference method. MIC values obtained with the reference method were then compared with those obtained with E-testing. The results were MIC50/90 (microg/mL) POS: 0.25/1, CAS: 0.06/4. Overall agreement with E-test: POS: 63.9%, CAS: 80.2%. None of the yeast isolates studied showed high MIC values for POS and CAS. Although it has some limitations, the E-test is a simple and fairly reliable system for determining the MICs of POS and CAS for yeast.