Availability and accessibility of a wide range of medications may be a contributing factor to rising medication-related overdose (OD) rates. Treatment for both suicide attempts (SAs) and ODs often occurs in the emergency department (ED), highlighting its potential as a screening and intervention point. The current study aimed to identify sociodemographic and clinical characteristics of individuals who reported SA via medication OD compared to other methods and to examine how these patients' suicide severity and behaviors differed over 12-month post-ED follow-up. Data were analyzed from Phases 1 and 2 of the Emergency Department Safety Assessment and Follow-up Evaluation multicenter study (N = 1376). Participants with a history of SA (n = 987) were categorized based on whether they indicated a past medication-related SA via OD. Of participants with history of SA, 62.7% (n = 619) reported medication OD for either their most serious or their most recent SA. Multivariate analyses indicated female birth sex, diagnosis of bipolar disorder, and having some college education were significantly associated with membership in the medication OD attempt group (p <0.05). Of those who attempted suicide over the 12-month follow-up, nearly 60% of participants in the medication OD attempt group reported a subsequent SA via OD over follow-up. However, nearly half (46.5%) of participants with no medication OD at baseline also reported medication OD at follow-up. Among patients presenting to the ED, females, individuals with bipolar disorder, and patients with a college education, respectively, may be at highest risk for SAs via medication OD. Prospectively, medication OD appears to be a frequent method, even among individuals with no prior attempt via OD, as demonstrated by the high percentage of patients who did not have a medication OD at baseline, but reported a medication OD during follow-up.