Antithrombotic management of STEMI patients with apical dysfunction, but without demonstrable thrombus, is controversial. Triple antithrombotic therapy (TATT, defined as the addition of oral anticoagulation to dual antiplatelet therapy, or DAPT) may be associated with increased bleeding, while DAPT alone may not adequately protect against cardio-embolic events. We undertook a dual-center study of anterior STEMI patients treated with primary PCI (pPCI) from 2013 to 2015 and presenting presumed new apical dysfunction. The Centre hospitalier de l'Université de Montréal (CHUM) uses a strategy of selective TATT, whereas the Centre hospitalier universitaire de Sherbrooke (CHUS) has favored ticagrelor-based DAPT for all patients since 2013. The primary composite outcome consisted of death, MI, stroke, revascularization, and BARC 3 to 5 bleeding up to 4-months follow-up. We identified 177 cases (69 CHUM; 108 CHUS). Baseline characteristics were similar and procedural success was high (97%). There was no difference in post-procedure LVEF (39 ± 9% vs 37 ± 9%) or the extent of apical dysfunction. The primary composite outcome occurred in 27% with the selective TATT strategy compared to 19% with ticagrelor-DAPT (p = 0.342). Thus, this retrospective dual-center analysis does not support a strategy of conventional TATT over ticagrelor-based DAPT for patients with apical dysfunction following anterior STEMI treated with pPCI. A pragmatic randomized trial is needed to provide a definitive answer to this clinical conundrum.