Power generation from low enthalpy geothermal resources using Organic Rankine Cycle systems is markedly influenced by the temperature level of the heat source and heat sink. During plant operation the actual temperature of the geofluid may be different from the value assumed in the design phase. In addition, the seasonal and daily variations of the ambient temperature greatly affect the power output especially when a dry condensation system is used. This paper presents a detailed off-design model of an Organic Rankine Cycle that includes the performance curves of the main plant components. Two capacitive components in the model have the key function of damping the temporary disequilibrium of mass and energy inside the system. Isobutane and R134a are considered as working fluids, mainly operating in subcritical and supercritical cycles, respectively. The off-design model is used to find the optimal operating parameters that maximize the electricity production in response to changes of the ambient temperatures between 0 and 30 °C and geofluid temperatures between 130 and 180 °C. This optimal operation strategy can be conveniently applied both to already existing plants and to the choice of new design plant configurations.