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Background and Objectives : ACS presents an acute manifestation of coronary artery disease and its treatment is based on timely interventional diagnostics and PCI. It has been known that the treatment and the outcomes are not the same for all the patients with ACS during the working day, depending on the availability of the procedures and staff. The aim of the study was to explore the differences in clinical characteristics and outcomes in patients admitted for ACS during on- and off-hours. Materials and Methods : The retrospective study included 1873 consecutive ACS patients admitted to a tertiary, university hospital that underwent coronary angiography and intervention. On-hours were defined from Monday to Friday from 07:30 h to 14:30 h, while the rest was considered off-hours. Results : There were more males in the off-hours group (on-hours 475 (56%) vs. off-hours 635 (62%); p = 0.011), while previous MI was more frequent in the on-hours group (on 250 (30%) vs. off 148 (14%); p < 0.001). NSTEMI was more frequent during on-hours (on 164 (19%) vs. off 55 (5%); p < 0.001), while STEMI was more frequent during off-hours (on 585 (69%) vs. off 952 (93%); p < 0.001). Patients admitted during on-hours had more multivessel disease (MVD) (on 485 (57%) vs. off 489 (48%); p = 0.006), as well as multivessel PCI (on 187 (22%) vs. off 171 (16%); p = 0.002), while radial access was preferred in off-hours patients (on 692 (82%) vs. off 883 (86%); p = 0.004). Left main PCI was performed with similar frequency in both groups (on 37 (4%) vs. off 35 (3%); p = 0.203). Death occurred with similar frequency in both groups (on 17 (2.0%) vs. off 26 (2.54%); p = 0.404), while major adverse cardio-cerebral events (MACCEs) were more frequent in the on-hours group (on 105 (12.4%) vs. off 70 (6.8%); p = 0.039) probably due to the more frequent repeated PCI (on 49 (5.8%) vs. off 27 (2.6%); p = 0.035). Conclusions : Patients admitted for ACS during working hours in a tertiary hospital present with more complex CAD, have more demanding interventions, and experience more MACCEs during follow-up mostly due to myocardial infarctions and repeated procedures.