We report the design and performance evaluation of novel pulse sequences for triple quantum filtered spectroscopy in homonuclear three spin-1/2 systems, employing isotropic mixing (IM) to excite triple quantum coherence (TQC). Our approach involves the generation of combination single quantum coherences (cSQC) from antisymmetric longitudinal or transverse magnetization components employing isotropic mixing (IM). cSQC's are then converted to TQC by a selective 180° pulse on one of the spins. As IM ideally causes magnetization to evolve under the influence of the spin coupling Hamiltonian alone, TQC is generated at a faster rate compared to sequences involving free precession. This is expected to be significant when the spins have large relaxation rates. Our approach is demonstrated experimentally by TQC filtered 1D spectroscopy on a 1H AX2 system (propargyl bromide in the presence of a paramagnetic additive), as well as a 31P linear AMX system (ATP in agar gel). The performance of the IM-based sequences for TQC excitation are compared against the standard three pulse sequence (Ernst et al., 1987) and an AX2 spin pattern recognition sequence (Levitt and Ernst, 1983). The latter reaches the unitary bound on TQC preparation efficiency starting from thermal equilibrium in AX2 systems, not considering relaxation. It is shown that in systems where spins relax rapidly, the new IM-based sequences indeed perform significantly better than the above two known TQC excitation sequences, the sensitivity enhancement being especially pronounced in the case of the proton system investigated. An overview of the differences in relaxation behavior is presented for the different approaches. Applications are envisaged to Overhauser DNP experiments and to in vivo NMR. © 2016 Elsevier Inc. All rights reserved.