Friction-based dampers are a valid solution for non-invasive seismic retrofitting interventions of existing structures, particularly reinforced-concrete (RC) structures. The design of friction-based dampers is challenging: underestimating the slip force prevents the full use of the potential of the device, which attains the maximum admissible displacement earlier than expected. By contrast, overestimating the slip force may cause delayed triggering of the device when the structure has suffered extensive damage. Therefore, designing the appropriate slip force is an optimization problem. The optimal slip force guarantees the highest inter-story drift reduction. The authors formulated the optimization problem for designing a specific class of friction-based dampers, the asymmetric friction connection (AFC), devised as part of the ongoing multidisciplinary Horizon 2020 research project e-SAFE (Energy and Seismic AFfordable rEnovation solutions). The seismic retrofitting technology involves the external application of modular prefabricated cross-laminated timber (CLT) panels on existing external walls. Friction dampers connect the CLT panels to the beams of two consecutive floors. The friction depends on the mutual sliding of two metal plates, pressed against each other by preloaded bolts. This study determines the optimal slip force, which guarantees the best seismic performance of an RC structural archetype. The authors investigate the nonlinear dynamic response of a coupled mechanical system (RC frame-friction damper) under a set of strong-motion earthquakes, using non-differential hysteresis models calibrated on the experimental cyclic responses. The solution of the optimization leads to the proposal of a preliminary simplified design procedure, useful for practitioners.