The assessment of a new or existing treatment or other intervention typically answers 1 of 3 central research-related questions: (1) “Can it work?” (efficacy); (2) “Does it work?” (effectiveness); or (3) “Is it worth it?” (efficiency or cost-effectiveness). There are a number of study designs that, on a situational basis, are appropriate to apply in conducting research. These study designs are generally classified as experimental, quasiexperimental, or observational, with observational studies being further divided into descriptive and analytic categories. This second of a 2-part statistical tutorial reviews these 3 salient research questions and describes a subset of the most common types of observational study designs. Attention is focused on the strengths and weaknesses of each study design to assist in choosing which is appropriate for a given study objective and hypothesis as well as the particular study setting and available resources and data. Specific studies and papers are highlighted as examples of a well-chosen, clearly stated, and properly executed study design type.