For the first time, surfactant-free platinum nanoparticles (Pt-NPs) prepared by pulsed laser ablation in liquids were employed in a real proton exchange membrane fuel cell (PEMFC). Laser-generated Pt-NPs show a larger size in comparison to a commercial Pt/C catalyst, being 6.6 nm for the laser-based and 3.8 nm for the reference, respectively. The laser-based Pt/C electrocatalyst was synthesized by colloidal deposition of laser-generated Pt-NPs onto carbonic Vulcan as support. The durability tests showed a much better stability of the laser-based catalyst in the electrochemical active surface area (ECSA) with an ECSA retention of 88% of its initial area. This better durability is probably caused by a reduced Pt dissolution rate which is higher for the reference catalyst containing NPs smaller than 3 nm. The occurrence of Pt dissolution is further indicated by X-ray photoelectron spectroscopy (XPS) of the electrodes after electrocatalytic testing showing no Pt signal in case of the reference catalyst. Performance tests of both PEMFC show a 20% higher mass-specific power density for the laser-based proton exchange membrane fuel cell.