For PCB layout of the PCA9544A, common PCB layout practices should be followed but additional concerns related to high-speed data transfer such as matched impedances and differential pairs are not a concern for I²C signal speeds. It is common to have a dedicated ground plane on an inner layer of the board and terminals that are connected to ground should have a low-impedance path to the ground plane in the form of wide polygon pours and multiple vias. By-pass and de-coupling capacitors are commonly used to control the voltage on the VCC terminal, using a larger capacitor to provide additional power in the event of a short power supply glitch and a smaller capacitor to filter out high-frequency ripple.

In an application where voltage translation is not required, all V_DPUX voltages and V_CC could be at the same potential and a single copper plane could connect all of pull-up resistors to the appropriate reference voltage. In an application where voltage translation is required, V_DPUM, V_DPU0, V_DPU1, V_DPU2, and V_DPU3 may all be on the same layer of the board with split planes to isolate different voltage potentials.

To reduce the total I²C bus capacitance added by PCB parasitics, data lines (SCn, SDn and INTn) should be a short as possible and the widths of the traces should also be minimized (e.g. 5-10 mils depending on copper weight).