Quasi-experimental studies evaluate the association between an intervention and an outcome using experiments in which the intervention is not randomly assigned. Quasi-experimental studies are often used to evaluate rapid responses to outbreaks or other patient safety problems requiring prompt, nonrandomized interventions. Quasi-experimental studies can be categorized into 3 major types: interrupted time-series designs, designs with control groups, and designs without control groups. This methods paper highlights key considerations for quasi-experimental studies in healthcare epidemiology and antimicrobial stewardship, including study design and analytic approaches to avoid selection bias and other common pitfalls of quasi-experimental studies. Infect Control Hosp Epidemiol 2016;1-6.