Methods and systems for enhanced defect detection based on images collected by at least two imaging detectors at different times are described. In some embodiments, the time between image measurements is at least 100 microseconds and no more than 10 milliseconds. In one aspect, one or more defects of interest are identified based on a composite image of a measured area generated based on a difference between collected images. In a further aspect, measurement conditions associated with the each imaged location are adjusted to be different for measurements performed by at least two imaging detectors at different times. In some embodiments, the measurement conditions are adjusted during the time between measurements by different imaging detectors. Exemplary changes of measurement conditions include environmental changes at the wafer under measurement and changes made to the optical configuration of the inspection system.