BACKGROUND: An individual's inability to self-identify or refusal to acknowledge an analgesic adverse drug event (ADE) lengthens the time to ADE treatment and resolution and may worsen the outcome. PURPOSE: The purpose was to describe how people who experienced an analgesic ADE during pain self-management respond to the event and to identify predictors of serious analgesic ADEs. METHODOLOGY: The design was a secondary data analysis. The sample consisted of 599 adult cases that had an analgesic ADE during pain self-management and reported their response to the ADE, the analgesic, a description of the ADE, demographic, and health data. Logistic regression was used to test predictors of serious versus nonserious analgesic ADEs. RESULTS: Three-fourth (75.5%) of cases indicated the ADE was easy to connect to the analgesic. The majority (72.6%) stopped the medication. Most (71.9%) talked with their provider. Serious ADEs such as gastrointestinal bleeding occurred in 16.2% of cases. Significant predictors of serious analgesic ADEs included less than a baccalaureate degree, male gender, and a higher Analgesic Adverse Drug Event Measure score. CONCLUSIONS: Adults who experience an analgesic ADE generally respond in an injury prevention way. A smaller group of individuals who experienced a serious analgesic ADE did not seem to differentiate between serious and nonserious ADEs. IMPLICATIONS: To promote safe pain management when prescribing new analgesics, providers should highlight common serious ADEs and instruct patients to contact them if an ADE emerges and to seek immediate care if they suspect a serious ADE.