Absorption of picoliter (pL) droplets into porous substrates is studied experimentally and numerically. In the case of pL droplets, major phenomena involved in the interaction between droplet and porous media develop at different time scales: spreading and wetting at microseconds, absorption and wicking at milliseconds, and evaporation at seconds. Therefore, one can decouple these processes to minimize the complexity of the study. A high-speed imaging system capable of 1 million frames per second is used to visualize individual droplets impacting, spreading, and imbibing on substrates. To simulate droplet dynamics, the governing equations for flow outside and inside porous media are proposed and solved using an in-house developed computational fluid dynamics solver. The simulation results are in good agreement with the experimental data. The effect of drop impact velocity and fluid properties on final dot shape in the porous substrates is investigated through a series of parametric numerical studies. (C) 2016 American Institute of Chemical Engineers AIChE J