High yield and integrity of placental RNA are crucial for placental transcriptomics studies. We assessed the effects of time to placental collection post-delivery; tissue storage, amount and method used for extraction; mode of delivery; and tissue type on total RNA yield. The optimal protocol for RNA extraction from placental tissue includes cryofreezing of the sample upon collection and RNA extraction from 50 mg of tissue using TRIzol reagent. Decidua yielded highest RNA quantity/mg of tissue, followed by villous tissue and the chorion. Comparisons with murine kidney and HEK293T show lower placental RNA yield, likely due to highly dense and heterogeneous tissue make-up and potential high placental nuclease activity.