Pharmacological reperfusion remains the primary strategy for ST-elevation myocardial infarction (STEMI) in low- and medium-income countries. Literature has reported inconsistent incidences and outcomes of failed thrombolysis (FT). This study aimed to identify the incidence, mortality outcomes and predictors of FT in STEMI pharmacological reperfusion. This single-centre retrospective cohort study analyzed data on consecutive STEMI patients who received thrombolytic therapy from 2016 to 2020 in a public tertiary hospital. Total population sampling was used in this study. Logistic regression analyses were used to assess independent predictors of the mortality outcomes and FT. We analyzed 941 patients with a mean age of 53.0 ± 12.2 years who were predominantly male (
n
= 846, 89.9%). The in-hospital mortality was 10.3% (
n
= 97). FT occurred in 86 (9.1%) patients and was one of the predictors of mortality (aOR 3.847,
p
< 0.001). Overall, tenecteplase use (aOR 1.749,
p
= 0.021), pre-existing hypertension (aOR 1.730,
p
= 0.024), history of stroke (aOR 4.176,
p
= 0.004), and heart rate ≥ 100 bpm at presentation (aOR 2.333,
p
< 0.001) were the general predictors of FT. The predictors of FT with streptokinase were Killip class ≥ II (aOR 3.197,
p
= 0.004) and heart rate ≥ 100 bpm at presentation (aOR 3.536,
p
= 0.001). History of stroke (aOR 6.144, p = 0.004) and heart rate ≥ 100 bpm at presentation (aOR 2.216,
p
= 0.015) were the predictors of FT in STEMI patients who received tenecteplase. Mortality following STEMI thrombolysis remained high in our population and was attributed to FT. Identified predictors of FT enable early risk stratification to evaluate the patients’ prognosis to manage them better.
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