Aim Octogenarian patients have higher mortality and morbidity rates after acute coronary syndromes. Risk factors for in‐hospital mortality in the primary percutaneous coronary intervention (PCI) era were underrepresented in previous studies. In the present study, we aimed to assess the risk factors of in‐hospital mortality after primary PCI in this population. Methods We analyzed 2353 patients who underwent primary PCI after ST segment elevated myocardial infarction (STEMI). Patients were divided into two groups according to aged: ≥80 years (octogenarian) and <80 years (control). Risk factors for in‐hospital mortality were analyzed in the whole group and octogenarian patients. Results We found that octogenarians have 10.6‐fold higher mortality risk after STEMI. After a univariate and multivariate analysis, acute stent thrombosis was the most explicit risk factor for in‐hospital mortality in the octogenarian group (OR 21.13, 95% CI 2.11–102.76, P < 0.001). Additionally, anterior myocardial infarction (OR 4.90, 95% CI 1.90–22.10, P = 0.04), ventricular arrhythmias (OR 15.64, 95% CI 2.81–87.12, P = 0.002), multivessel disease (OR 6.5, 95% CI 1.11–38.85, P = 0.04), ejection fraction <30% (OR 1.24, 95% CI 0.26–6.00, P = 0.04) and KILLIP score ≥2 (OR 1.20, 95% CI 0.20– 7.41, P = 0.01) were also significantly associated with mortality. Conclusions Acute stent thrombosis, anterior MI, heart failure, low ejection fraction, ventricular arrhythmias and multivessel disease are the independent risk factors for in‐hospital mortality among octogenarian patients after primary PCI. Geriatr Gerontol Int 2017; 17: 584–590.