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Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years; IQR [2.4-5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0-9]) in women and 5.0 (IQR [1-11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6-17]) in women and 10 (IQR [6-15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33; IQR [1.02-1.74]). Women with MVD had CDMI more often than all other groups (p<0.001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43%; p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion : Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS>8. Observed differences in P2Y 12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation., Competing Interests: Disclosure: SB is a committee member of ANZET, CSANZ, EAPCI, WIN-APSIC and Women-as-One and reports speaker fees/honoraria from AstraZeneca, Women-as-One, Pfizer and Novartis outside of this work. LT is a board member of CNAZ and chair of the AAN. SZ reports consulting fees from Medtronic and speakers fees from Boehringer Ingelheim and AstraZeneca outside of this work. All other authors have no conflicts of interest to declare. Data availability: The data that support the findings of this study are available on request from the corresponding author. Authors’ contributions: Conceptualisation: SB, SZ, LT, CM, SL, JF; data curation: SB, IMS, WY, HI, AM, TN, KPR, CM, SL, JF; formal analysis: SB, TN, KPR, CM, SL, JF; funding acquisition: N/A; investigation: SB, JF, IMS, TN; methodology: SB, CM, SL, CPJ, JF, LT, TN; project administration: SB, TN, JF; resources: N/A; software: N/A; supervision: JF, CPJ; validation: N/A; visualisation: SB, SZ, KPR, JF; writing – original draft preparation: SB, JF, SZ; writing – review & editing: all authors. Ethics: This study was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Approval was granted by the Ethics Committee of Southwest Sydney Local Health District Human Research Ethics Committee (QA08/034). Consent: Written informed consent was obtained if experimentation with human subjects was conducted. Included patients gave informed consent for data use in publications., (Copyright © 2023, Radcliffe Cardiology.)