A frequency-domain approach to efficiently simulate and minimize the crosstalk between high speed interconnects is proposed in this paper. Several methods for modeling coupled microstrip transmission lines are discussed. Several possible simulation strategies are also considered. A straightforward yet rigorous frequency-domain approach is followed. This approach can be used for linearly and non-linearly terminated microstrip coupled lines, since it exploits the harmonic balance technique. A typical example of microstrip interconnects is simulated and the results are compared with those obtained in previous work by other authors using time-domain methods. The simulation method proposed in this work yields good accuracy. A crosstalk minimization problem is formulated and solved following the method proposed.ITESO, A.C.