Disclosed is a method for initializing a dosing unit (20) of an ambulatory infusion system, the method including carrying out a first priming routine. The first priming routine includes: providing the dosing unit (20) with a dosing chamber (202) having a minimal dosing chamber volume, a draining valve (205) being closed and a filling valve (204) being open. The first priming routine further includes measuring an initial reservoir fluid pressure p 2 and computing, a first priming volume v 1 . The method further includes increasing the dosing chamber volume by the first priming volume v 1 , with the first priming volume v 1 being computed such that a reservoir coupling conduit is filled with liquid drug substantially completely at the end of the dosing chamber volume increasing. The first priming routine further includes closing the filling valve (204) and opening the draining valve (205) and emptying the dosing unit (20) by decreasing the dosing chamber volume to the minimal dosing chamber volume. Disclosed are further a control unit for controlling operation of a dosing unit as well as an ambulatory infusion device.