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During the COVID-19 pandemic, the pharmaco-invasive approach in the management of ST Elevation Myocardial Infarction (STEMI) played a vital role in saving many lives. A retrospective observational study was conducted wherein 134 patients presenting with STEMI between (Dec 2019–Mar 2022) were thrombolysed with either streptokinase or tenecteplase in a centre where primary PCI was not available. There was no significant difference in the outcomes and their predictors between the SK and TNK groups. A prospective study with a larger sample size in the Indian population will be able to provide more substantial and promising results for further interventions.