The design optimization of H5, H6, Neutral Point Clamped, Active-Neutral Point Clamped and Conergy-NPC transformerless Photovoltaic inverters is presented in this paper. The components reliability in terms of the corresponding malfunctions, affecting the Photovoltaic inverter maintenance cost during the operational lifetime period of the Photovoltaic installation, is also considered in the optimization process. According to the results of the proposed design method, different optimal values of the Photovoltaic inverter design variables are derived for each Photovoltaic inverter topology and installation site. The H5, H6, Neutral Point Clamped, Active-Neutral Point Clamped and Conergy-NPC Photovoltaic inverters designed using the proposed optimization process feature lower Levelized Cost Of generated Electricity and lifetime cost, longer Mean Time Between Failures and inject more Photovoltaic-generated energy into the electric grid than their non-optimized counterparts, thus maximizing the total economic benefit obtained during the operational time of the Photovoltaic system.