Objectives The study reports the final 5-year safety and effectiveness outcomes of the novel abluminal groove-filled biodegradable polymer-coated FIREHAWK sirolimus-eluting stent in a large patient cohort. Background The TARGET clinical program was conducted to evaluate the performance of the FIREHAWK stent, and this objective performance criterion study pooled long-term safety and efficacy data from three TARGET trials for greater statistical power to analyze low-frequency events. Methods Patient-level pooled data from 1,007 individuals in the TARGET I randomized controlled trial (n = 227), TARGET I long lesion cohort (n = 50), and TARGET II registry (n = 730) were prospectively collected and analyzed. The primary endpoint, target lesion failure (TLF), was defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI), and ischemia-driven indicated target lesion revascularization (ID-TLR) at 5 years. All patients were exclusively treated with the FIREHAWK stent and had annual follow-up visits for up to 5 years. Results Among 947 patients (94.0%) who completed the 5-year clinical follow-up, the 5-year TLF event rate was 8.1%; the events included 18 cardiac deaths, 36 TV-MIs, and 33 ID-TLRs. Only four (0.4%) very late probable or definite stent thrombosis events were observed beyond 1 year after stent implantation. In the subgroup analysis, lesion length >= 30 mm was associated with higher long-term TLF incidence, while the use of a predilation-sizing-postdilation technique showed no significant effect on long-term outcomes. Conclusions Five-year results demonstrate the continuing safety and efficacy of the FIREHAWK Stent, with relatively lower incidence of thrombotic events.