Background: Observational studies using real-world data (RWD) can address gaps in knowledge on deprescribing medications but are subject to methodological issues. Limited data exist on the methods employed to use RWD to measure the effects of deprescribing.

Objective: To describe methodological approaches used in observational studies of deprescribing medications in older adults.

Method: We conducted a systematic review in Medline for observational studies published in English (01/01/2000-09/14/2023) that examined the health effects of medication deprescribing in older adults. We described study characteristics and methods, focusing on the operationalization of deprescribing as an exposure and potential time-related biases.

Results: Forty-five studies were included, representing a variety of drug classes (e.g., statins, aspirin, bisphosphonates) and diseases. Most studies adequately addressed potential time-related biases. The definition of deprescribing was not clearly defined in 12 studies. There was heterogeneity regarding the minimum duration of time that qualified as deprescribing, even within a drug class; fewer than one-third of studies provided a justification for these definitions.

Conclusion: Observational studies are common to examine the effects of deprescribing; however, there were inconsistencies in measuring deprescribing and a lack of transparency in reporting. There is a need for minimum sufficient reporting criteria for observational studies on deprescribing.