Introduction: ACEIs are the most commonly prescribed antiHTN drugs, but side effects may prompt additional therapy resulting in a prescribing cascade. We aimed to identify potential ACEI-induced prescribing cascades using high throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) national samples of Medicare FFS beneficiaries, we identified new ACEI users aged ≥66 y with continuous enrollment for ≥360 days pre- and ≥180 days post-ACEI initiation. We screened for initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of ACE initiation, generating sequence ratios (SRs) representing the proportions of ACEI initiators starting the marker class after, vs before, the ACEI. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs >1 considered statistically significant. Results: We identified 297,410 ACEI initiators (mean ± SD age, 76.1 ± 7.5 y; 59% women, 88% HTN). Of 446 ‘marker’ classes studied, and excluding other antiHTN classes, we identified 110 statistically significant signals indicative of potential prescribing cascades. The 30 strongest prescribing cascade signals (by aSR) are summarized (Figure) and included decongestant nasal preparations and monoamine oxidase B inhibitors. Conclusion: We identified potential prescribing cascade signals reflecting known and possibly underrecognized ACEI adverse events in this Medicare cohort. Additional research is needed to determine impact of these cascades on patient outcomes.