The design optimization of H5, H6, neutral point clamped, active-neutral point clamped, and conergy-NPC transformerless photovoltaic (PV) inverters is presented in this paper. The components reliability in terms of the corresponding malfunctions, affecting the PV inverter maintenance cost during the operational lifetime period of the PV installation, is also considered in the optimization process. According to the results of the proposed design method, different optimal values of the PV inverter design variables are derived for each PV inverter topology and installation site. The H5, H6, neutral point clamped, active-neutral point clamped and conergy-NPC PV 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 PV-generated energy into the electric grid than their nonoptimized counterparts, thus maximizing the total economic benefit obtained during the operational time of the PV system.