The new‐user design has been widely used in pharmacoepidemiology. By following patients from the initiation of a treatment, the new‐user design has several advantages over designs that begin follow‐up on prevalent users. The new‐user design allows study of the full time course of outcome risk after treatment initiation, with representation of early and late events. It also ensures appropriate temporal ordering of baseline confounders, exposures, and outcomes, avoiding adjustment for intermediate variables that may have been affected by treatment. Coupled with an active‐comparator design, new‐user approaches can mitigate the potential for immortal time‐bias and confounding by indication. The active comparator new‐user design helps to articulate clearly a causal question about the benefits and harms of starting a particular intervention in a more real‐world setting. These theoretical and conceptual advantages have led to the recommendation that such designs should be a default approach for comparative effectiveness research studies.