Methods and systems for detecting defects on a wafer are provided. One method includes acquiring output for a wafer generated by an inspection system. Different dies are printed on the wafer with different process conditions. The different process conditions correspond to different failure modes for the wafer. The method also includes comparing the output generated for a first of the different dies printed with the different process conditions corresponding to a first of the different failure modes with the output generated for a second of the different dies printed with the different process conditions corresponding to a second of the different failure modes opposite to the first of the different failure modes. In addition, the method includes detecting defects on the wafer based on results of the comparing step.