Chemical exchange saturation transfer (CEST) imaging depends on the performance of radiofrequency saturation during the experiment. Scanner specifications, in particular limited pulse width and duty‐cycle, and specific absorption rate guidelines restrict the full exploitation of CEST effects in clinical MR systems. The purpose of this study was to optimize techniques for effective pulse train presaturation for CEST imaging in a whole‐body MR scanner. Theoretical analysis and simulations of the spectral properties of radiofrequency pulse trains demonstrated the significance of pulse width τP and interpulse delay τD for effective and selective labeling of a chemically exchanging proton pool. CEST experiments with model solutions, e.g., creatine dissolved in water, showed best performance of pulse trains with τP = τD = 100 msec, regarding minimum direct water saturation in z‐spectra and distinct magnetization transfer ratio asymmetry that can be determined quantitatively. Saturation efficiency of trains of Gaussian‐shaped radiofrequency pulses using this timing was evaluated in MR imagers with field strengths of 1.5, 3, and 7 T. The proposed saturation pulse train does not require hardware modifications, offers low specific absorption rate, and can be used in a standard clinical setup. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.