Background Evidence suggests that acute coronary syndrome (ACS) is underdiagnosed in sub-Saharan Africa. Triage-based interventions have improved ACS diagnosis and management in high-income settings but have not been evaluated in sub-Saharan African emergency departments (EDs). Our objective was to estimate the effect of a triage-based screening protocol on ACS diagnosis and care in a Tanzanian ED. Methods and Results All adults presenting to a Tanzanian ED with chest pain or shortness of breath were prospectively enrolled. Treatments and clinician-documented diagnoses were observed and recorded. In the preintervention phase (August 2018 through January 2019), ACS testing and treatment were dictated by physician discretion, as per usual care. A triage-based protocol was then introduced, and in the postintervention phase (January 2019 through October 2019), research assistants performed ECG and point-of-care troponin I testing on all patients with chest pain or shortness of breath upon ED arrival. Pre-post analyses compared ACS care between phases. Of 1020 total participants (339 preintervention phase, 681 postintervention phase), mean (SD) age was 58.9 (19.4) years. Six (1.8%) preintervention participants were diagnosed with ACS, versus 83 (12.2%) postintervention participants (odds ratio [OR], 7.51; 95% CI, 3.52-19.7; P<0.001). Among all participants, 3 (0.9%) preintervention participants received aspirin, compared with 50 (7.3%) postintervention participants (OR, 8.45; 95% CI, 3.07-36.13; P<0.001). Conclusions Introduction of a triage-based ACS screening protocol in a Tanzanian ED was associated with significant increases in ACS diagnoses and aspirin administration. Additional research is needed to determine the effect of ED-based interventions on ACS care and clinical end points in sub-Saharan Africa.