This systematic review and meta-analysis aimed to evaluate patients with acute ST-segment elevation myocardial infarction (STEMI) who were admitted during off-hours and treated with primary angioplasty associated with an increased risk of mortality compared with those admitted during regular working hours. We performed a systematic literature search using PubMed, SCOPUS, Europe PMC, and Cochrane CENTRAL databases that was finalized on March 15, 2021. The primary outcome was mortality comprising early (in-hospital), midterm (30 days to 1 year), and long-term mortality (>1 year). A total of 384,452 patients from 56 studies were included. The overall mortality of acute STEMI patients admitted during off-hours and regular hours were 6.1 and 6.7%, respectively. Patients admitted during off-hours had similar risk of early, midterm, and long-term mortality compared to those admitted during regular working hours ([relative risk or RR = 1.07, 95% confidence interval or CI, 1.00-1.14,  = 0.06;  = 45%,  = 0.0009], [RR = 1.00, 95% CI, 0.95-1.05,  = 0.92;  = 13%,  = 0.26], and [RR = 0.95, 95% CI, 0.86-1.04,  = 0.26;  = 0%,  = 0.76], respectively). Subgroup analyses indicated that the results were consistent across all subgroups ([women vs. men], [age >65 years vs. ≤65 years], and [Killip classification II to IV vs. Killip I]). Funnel plot was asymmetrical. However, Egger's test suggests no significance of small-study effects (  = 0.19). This meta-analysis showed that patients with acute STEMI who were admitted during off-hours and treated with primary angioplasty had similar risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.