An approach for recording four-dimensional (4D) methyl H-1-C-13-C-13-H-1 NOESY spectra with high resolution and sensitivity is presented and applied to Malate Synthase G (723 residues, 82 kDa). Sensitivity and resolution have been optimized using a highly deuterated, methyl-protonated sample in concert with methyl-TROSY, sparse data sampling in the three indirect dimensions, and 4D spectral reconstruction using multidimensional decomposition (MDD). A sparse data acquisition protocol is introduced that ensures that sufficiently long indirect acquisition times can be employed to exploit the decreased relaxation rates associated with methyl-TROSY, without increasing the duration of the 4D experiment beyond acceptable measurement times. In this manner, only a fraction (similar to30%) of the experimental data that would normally be needed to achieve a spectrum of high resolution is acquired. The reconstructed 4D spectrum is of similar resolution and sensitivity to three-dimensional (3D) C-13-edited NOE spectra, is straightforward to analyze, and resolves ambiguities that emerge when 3D data sets only are considered.