The emergence of three-dimensional imaging in the field of medical ultrasound imaging has greatly increased the number of transmissions needed to insonify a whole volume. With a large number of transmissions comes a low image frame rate. When using classical transmission techniques, as in two-dimensional imaging, the frame rate becomes unacceptably low, prompting the use of alternative transmission patterns that require less time. One alternative is to use a multi-line transmission (MLT) technique which consists of transmitting several pulses simultaneously in different directions. Perturbations appear when acquiring and beamforming the signal in the direction of one pulse because of the pulses sent in other directions. The edge waves from the pulses transmitted in a different direction add to the signal transmitted in the direction of interest, resulting in artifacts in the final image. Taking advantage of the nonlinear propagation of sound in tissue, the second-harmonic signal can be used with the MLT technique. The image obtained using the second-harmonic signal, compared with an image obtained using the fundamental signal, should have reduced artifacts coming from other pulses transmitted simultaneously. Simulations, backed up by experiments imaging a wire target and an in vivo left ventricle, confirm that the hypothesis is valid. In the studied case, the perturbations appear as an increase in the signal level around the main echo of a point scatterer. When using the fundamental signal, the measured amplitude level of the perturbations was approximately -40 dB compared with the maximum signal amplitude (-27 dB in vivo), whereas it was around -60 dB (-45 dB in vivo) for the second-harmonic signal. The MLT technique encounters limitations in the very near field where the pulses overlap and the perturbation level also increases for images with strong speckle and low contrast.