Changes in the excitability of the cortical projections to muscles in the upper and lower limbs can be induced in the intact human by paired associative stimulation (PAS). An interstimulus interval (ISI) of 25 ms between peripheral nerve and transcranial magnetic stimuli has been found to be effective when targeting hand muscles. The optimal ISI to induce plasticity changes in the cortical projections to lower limbs is still not well established. The purpose of this study was twofold: first, to investigate the effect of PAS with four different ISIs based on the individual latency of the sensory evoked potential (SEP plus 6, 12, 18 and 24 ms) and second, to evaluate the repeatability of the established optimal ISI. Transcranial magnetic stimulation was used to measure changes in the motor evoked potentials (MEPs) of the soleus (SOL) muscle before and after the PAS interventions. Significant increases in the amplitude of SOL MEPs (88 %) were attained with an ISI of SEP latency plus 18 ms (P32 + 18 ms). The PAS effect was long-lasting, input-specific and supraspinal in origin. The intraclass correlation coefficient to test the repeatability of the PAS intervention with the optimal ISI was 0.85. The results show that the excitability of cortical projections to the soleus muscle can be repeatedly increased after PAS with an optimal ISI of SEP plus 18 ms.