Microfluidics is a technology that manipulates liquids on the scales ranging from microliters to femtoliters. Such low volumes require precise control over pressures that drive their flow into the microfluidic chips. This article describes a custom-built pressure controller for driving microfluidic chips. The pressure controller features piezoelectrically controlled pressure regulation valves. As an open-source system, it offers high customizability and allows users to modify almost every aspect. The cost is roughly a third of what similar, alternative, commercially available piezoelectrically controlled pressure regulators could be purchased for. The measured output pressure values of the device vary less than 0.7% from the device’s reported pressure values when the requested pressure is between −380 and 380 mbar. Importantly, the output pressure the device creates fluctuates only ±0.2 mbar when the pressure is cycled between 10 and 500 mbar. The pressure reading accuracy and stability validation suggest that the device is highly feasible for many advanced (low-pressure) microfluidic applications. Here, we compare the main features of our device to commercially and non-commercially available alternatives and further demonstrate the device’s performance and accessibility in successful microfluidic hydrodynamic focusing (MHF)-based synthesis of large unilamellar vesicles (LUVs).