Methods and systems for detecting defects on a wafer are provided. One system includes one or more computer subsystems configured for generating a rendered image based on information for a design printed on the wafer. The rendered image is a simulation of an image generated by the optical inspection subsystem for the design printed on the wafer. The computer subsystem(s) are also configured for comparing the rendered image to an optical image of the wafer generated by the optical inspection subsystem. The design is printed on the wafer using a reticle. In addition, the computer subsystem(s) are configured for detecting defects on the wafer based on results of the comparing.