(1) Background: Percutaneous Coronary Interventions (PCI) in patients with acute coronary syndrome (ACS) are performed with titanium-nitride-oxide-coated stents (TiNOS) or drug-eluting stents (DES). This prospective systematic literature review (SLR) of prospective, randomized, controlled trials (RCTs) showed TiNOS is non-inferior to DES in major adverse cardiac events (MACE) rates and presents a lower risk of recurrent myocardial infarction (MI) at 1-year follow-up. (2) Methods: The previously described SLR and meta-analysis protocol, per PRISMA, Cochrane methods, and GRADE, applied here to 5-year follow-up outcomes. (3) Results: Three RCTs were eligible, comprising 1,620 patients with TiNOS vs. 1,123 with DES. The pooled risk ratios (RRs) and 95% confidence intervals were: MACE 0.82 [0.68, 0.99], MI 0.58 [0.44, 0.78], cardiac death (CD) 0.46 [0.28, 0.76], ischemia-driven target lesion re-vascularization (TLR) 1.03 [0.79, 1.33], probable or definite stent thrombosis (ST) 0.32 [0.21, 0.59], and all-cause mortality (TD) 0.84 [0.63, 1.12]. Evidence certainty was high in MACE, CD, MI, and ST. Certainty was moderate in TLR and TD. (4) Conclusions: TiNOS in ACS at 5-year follow-up appears safer than DES and equally efficacious. Stratified pooled outcomes by clinical presentation would facilitate clinical validity benchmarking and generalization to target populations.