Early detection of systematic patterning problems can provide a major boost for a technology team. Often in the past, these type defects might only be detected after functional test and subsequent failure analysis. At this point, three to six months of process development time have been lost and three to six months of defective hardware have been wasted. In this paper, a methodology for in-line detection of systematic patterning problems using E-beam hot spot inspection (EBHI) is introduced. Pattern simulation tools and other sources are used to recommend X, Y locations with challenging geometries for evaluation. EBHI evaluates the patterning capability for these locations using modulated wafers. A multifunction team addresses the hot spots that fail within the process window. EBHI is then used to evaluate the solutions proposed by this team. Often, additional data is necessary to determine the full yield impact. This methodology provided tremendous value for IBM's 22 nm SOI technology. Several examples illustrating this point are presented. Line monitoring after the process windows have been established is also discussed.