Background: The randomized DAPA trial (Defibrillator After Primary Angioplasty) aimed to evaluate the survival benefit of prophylactic implantable cardioverter defibrillator (ICD) implantation in early selected high-risk patients after primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction. Methods: A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk patients with primary percutaneous coronary intervention, based on one of the following factors: left ventricular ejection fraction <30% within 4 days after ST-segment–elevation myocardial infarction, primary ventricular fibrillation, Killip class ≥2 or TIMI (Thrombolysis in Myocardial Infarction) flow <3 after percutaneous coronary intervention. ICD was implanted 30 to 60 days after MI. Primary end point was all-cause mortality at 3 years follow-up. The trial prematurely ended after inclusion of 266 patients (38% of the calculated sample size). Additional survival assessment was performed in February 2019 for the primary end point. Results: A total of 266 patients, 78.2% males, with a mean age of 60.8±11.3 years, were enrolled. One hundred thirty-one patients were randomized to the ICD arm and 135 patients to the control arm. All-cause mortality was significant lower in the ICD group (5% versus 13%, hazard ratio, 0.37 [95% CI, 0.15–0.95]) after 3 years follow-up. Appropriate ICD therapy occurred in 9 patients at 3 years follow-up (5 within the first 8 months after implantation). After a median long-term follow-up of 9 years (interquartile range, 3–11), total mortality (18% versus 38%; hazard ratio, 0.58 [95% CI, 0.37–0.91]), and cardiac mortality (hazard ratio, 0.52 [95% CI, 0.28–0.99]) was significant lower in the ICD group. Noncardiac death was not significantly different between groups. Left ventricular ejection fraction increased ≥10% in 46.5% of the patients during follow-up, and the extent of improvement was similar in both study groups. Conclusions: In this prematurely terminated and thus underpowered randomized trial, early prophylactic ICD implantation demonstrated lower total and cardiac mortality in patients with high-risk ST-segment–elevation myocardial infarction treated with primary percutaneous coronary intervention. Registration: URL: https://www.trialregister.nl ; Unique identifier: Trial NL74 (NTR105).