Abstract Introduction There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries (HICs). Global clinical guidelines are pivotal to the delivery of evidence based cardiovascular care, however their applicability to populations in SSA remains unclear. Purpose To evaluate the extent to which populations from SSA contribute to pharmacotherapeutic randomised clinical trials informing international ACS and HF clinical guidelines. Methods We extracted details on pharmacotherapeutic randomised control trials (RCTs) contributing to Class I or II guideline recommendations from the 2023 European Society of Cardiology (ESC) guidelines for ACS and the 2021 ESC guidelines for HF. Data on RCTs contributing to these guidelines were extracted from the ClinicalTrials.gov or published articles. We analysed the proportion of RCTs which had a contribution from countries in each World Bank income group. Then we specifically assessed the contribution of SSA countries to clinical trials and analysed temporal trends. Results Of 119 RCTs from the ESC HF guidelines and the 343 pharmacotherapy RCTs from the ESC ASC guidelines 75.9% were exclusively conducted in high-income countries, 22.2% of the trials included at least one site from a middle-income country and none included sites from a low-income country (figure 1). The global distribution of HF (figure 2a) and ACS (figure 2b) pharmacotherapy guidelines is demonstrated in figure 2. The only country represented from SSA was South Africa which is an upper middle-income country. A site from South Africa was included in 17 (14.2%) HF RCTs and 28 (8.2%) ACS RCTs. There has been a significant increase in the proportion HF RCTs conducted in SSA, increasing from 2.6% between 1990 and 1999 to 50% since 2020 (OR 28.8, 95% CI 2.6 – 983.4, p-value for trend< 0.0001). For ACS RCTs, the proportion of trials conducted in SSA increased from 1.8% pre 1990 to 23.4% during 2000-2009 (OR 15.9, 95% CI 4.2 - 112.9, p value for trend = 0.003) then declined to 11.3% from 2010-2019. Conclusions There is a marked under-representation of SSA countries in ACS and HF pharmacotherapy RCTs, despite the region's escalating cardiovascular disease burden. South Africa is the sole contributor from the region, with all other SSA countries absent. This finding could potentially affect the applicability and generalisability of global guidelines to populations in SSA with distinct clinical presentations and healthcare challenges.Figure 1 Figure 2