The transesterification of different vegetable oils to biodiesel under thermal and ultrasound activation was carried out using commercial solid base CaO (CS) and microcrystalline CaO particles (MS) catalysts. The last sample was prepared from the first one using a simple, green and reproducible method and characterized by XRD, LLS, DRIFT and DR-UV–Vis techniques. Each catalyst (i.e., CaO (CS) and CaO (MS)) was used as well, freshly pre-activated at 623, 788 and 873 K or ultrasonicated at room temperature, in methanol. Ultrasounds activation of the reactant molecules led to conversions of the vegetable oil of 97% at 348 K for a molar ratio of methanol to vegetable oil of 4:1. Ultrasonicated catalysts can be reused for several runs without significant deactivation.