Timely reperfusion through primary percutaneous coronary intervention (PCI) is the gold standard treatment for ST-elevation myocardial infarction (STEMI). However, delays during off-hours—nights, weekends, and public holidays—may influence door-to-balloon (DTB) time, resource availability, and clinical outcomes. This study evaluates the impact of emergency PCI protocols during off-hours in a tertiary care system over 14 months, comparing procedural efficiency, mortality, and major adverse cardiac events (MACE) between regular-hours and off-hours presentations. A total of 246 patients were enrolled (110 during regular hours, 136 during off-hours). Results indicate a statistically significant increase in DTB time during off-hours (median 82 min vs 64 min) and slightly higher 30-day mortality (7.3% vs 4.5%). However, structured off-hours activation protocols reduced delays by 23% compared to the historical baseline. Findings suggest off-hours PCI can achieve comparable outcomes when optimized through rapid team activation models.