Background: Early Psychological First Aid (PFA) has been widely recommended for preventing posttraumatic stress disorder (PTSD). However, its lack of empirical evidence of safety and effectiveness has been criticized. Objectives: To assess the effectiveness of PFA-ABCDE, an original PFA protocol, for preventing PTSD one month after the intervention and decreasing PTSD symptoms at one and six months of follow up. Methods: We assessed the eligibility of 1,140 adult survivors of recent trauma (≤ 72 hours) consulting five emergency departments in Chile. Two hundred twenty-one were randomized to receive either PFA-ABCDE (active listening, breathing retraining, categorization of needs, referral to ancillary services, and psychoeducation) or only psychoeducation. We used the Composite International Diagnostic Interview (CIDI) to assess PTSD diagnosis. The Posttraumatic Checklist (PCL), the Beck Depression Inventory-II (BDI-II), and a 0–10 points analogue visual scale were used to assess PTSD symptoms, depressive symptoms, and immediate distress relief after the intervention. Results: We found no difference between the experimental and control groups in the frequency of PTSD one month after the intervention (PFA-ABCDE = 23/76 [30.3%], psychoeducation = 18/75 [24.0%], adjusted odds ratio = 1.39, 95% confidence interval = 0.63–3.07, p = .408). Immediately after the intervention, participants who received PFA-ABCDE reported greater distress relief (PFA-ABCDE mean = 9.06, psychoeducation mean = 8.55, Cohen’s d = 0.30, p = .038). Fewer PTSD symptoms were reported by those who received PFA-ABCDE one month after the intervention (PFA-ABCDE mean = 36.26, psychoeducation mean = 43.62, Cohen’s d = 0.42, p = .033). We found no difference in depressive symptoms at one-month follow up (p = .713) nor in PTSD symptoms six months after the intervention (p = .986). Conclusions: PFA-ABCDE does not prevent PTSD diagnosis, but it provides immediate distress relief and decreases PTSD symptoms in the short term.