Quality control (QC) procedures incorporating patient means, or average of normals (AoN) algorithms, have been used in hematology laboratories and large reference laboratories for decades to monitor analytical processes during the periods between the testing of reference sample QC materials. With the advent of middleware that includes AoN capability, these QC procedures are now available to many more laboratories, including medium-sized hospital laboratories. AoN procedures can improve the control of tests that have low “sigma-metrics,” such as electrolytes, where relatively low numbers of patient results can be averaged to provide a high probability of detecting medically significant errors. QC of nearly one-third of the tests whose AoN capabilities have been studied would possibly benefit from AoN procedures in medium-sized laboratories. To obtain satisfactory performance, laboratories must tailor the applications of AoN procedures to their particular volumes and test characteristics.