What accounts for the Right Hemisphere (RH) functional superiority in visual change detection? An original task which combines one-shot and divided visual field paradigms allowed us to direct change information initially to the RH or the Left Hemisphere (LH) by deleting, respectively, an object included in the left or right half of a scene presented centrally. We manipulated the perceptual salience and semantic relevance of the change as well as the duration of the Inter-Stimulus Interval (ISI) between the scenes in order to clarify the role of the RH in memory and attention processes, and to explore whether lengthening the ISI would enhance the contribution of the LH. When analyzing data collapsed over the two levels (high vs. low) of salience and of relevance, changes were better detected in the left visual field (lvf) than in the right visual field (rvf) in the case of a short ISI, while no difference emerged in the case of a long ISI. Moreover, lengthening the ISI resulted in a performance decrement in the lvf, both for accuracy and response speed. The fact that the RH superiority was limited to short intervals indicates that stimulus-driven orienting contributes more than perceptual processing to this hemispheric asymmetry. When considering perceptual and semantic properties of the change, the effect of the ISI duration seemed to specifically emerge in the case of low relevance, with an enhancement of accuracy in the rvf when comparing the long with the short ISI. This suggests that the ISI influence on hemispheric performance operates on different levels.