Dynamic contrast-enhanced magnetic resonance imaging is increasingly applied for tumour diagnosis and early evaluation of therapeutic responses over time. However, the reliability of pharmacokinetic parameters derived from DCE-MRI is highly dependent on the experimental settings. In this study, the effect of sampling frequency (f(s)) and duration on the precision of pharmacokinetic parameters was evaluated based on system identification theory and computer simulations. Both theoretical analysis and simulations showed that a higher value of the pharmacokinetic parameter K(trans) required an increasing sampling frequency. For instance, for similar results, a relatively low f(s) of 0.2 Hz was sufficient for a low K(trans) of 0.1 min⁻¹, compared to a high f(s) of 3 Hz for a high K(trans) of 0.5 min⁻¹. For the parameter v(e), a decreasing value required a higher sampling frequency. A sampling frequency below 0.1 Hz systematically resulted in imprecise estimates for all parameters. For the K(trans) and v(e) parameters, the sampling duration should be above 2 min, but durations of more than 7 min do not further improve parameter estimates.