An observational study is an attempt to infer the effects caused by treatments when it is unethical or impractical to assign individuals to treatments at random, as would be done in a randomized experiment. Three observational studies are described. The first, from the medical literature, concerns the possible effects of general anesthesia on the risk of dementia. Of medium size, this study matched each of 54,996 treated individuals to 5 untreated controls in blocks of size six, making 329, 976 = 6 × 54, 996 individuals in total. The other two studies are of similar structure, but they are simpler and smaller, with public data that is available to the reader for reanalysis in the R package iTOS. These two smaller studies will illustrate concepts throughout the book. Both studies concern the effects of consuming alcohol. One study asks whether light daily alcohol consumption causes a desirable increase in HDL cholesterol, the so-called “good cholesterol.” The second study asks whether frequent binge drinking causes an undesirable increase in blood pressure. These examples exemplify methodology, and that is their sole function. They do not address the most important effects of alcohol, such as its role in causing cancer, and its total effect on longevity, effects that are mentioned here only briefly.