OBJECTIVE: The quick Sequential Organ Failure Assessment (qSOFA) is developed as a tool to identify patients with infection with increased risk of dying from sepsis in non-intensive care unit settings, like the emergency department (ED). An abnormal score may trigger the initiation of appropriate therapy to reduce that risk. This study assesses the risk of a treatment paradox: the effect of a strong predictor for mortality will be reduced if that predictor also acts as a trigger for initiating treatment to prevent mortality. DESIGN: Retrospective analysis on data from a large observational cohort. SETTING: ED of a tertiary medical centre in the Netherlands. PARTICIPANTS: 3178 consecutive patients with suspected infection. PRIMARY OUTCOME: To evaluate the existence of a treatment paradox by determining the influence of baseline qSOFA on treatment decisions within the first 24 hours after admission. RESULTS: 226 (7.1%) had a qSOFA ≥2, of which 51 (22.6%) died within 30 days. Area under receiver operating characteristics of qSOFA for 30-day mortality was 0.68 (95% CI 0.61 to 0.75). Patients with a qSOFA ≥2 had higher odds of receiving any form of intensive therapy (OR 11.4 (95% CI 7.5 to 17.1)), such as aggressive fluid resuscitation (OR 8.8 95% CI 6.6 to 11.8), fast antibiotic administration (OR 8.5, 95% CI 5.7 to 12.3) or vasopressic therapy (OR 17.3, 95% CI 11.2 to 26.8), compared with patients with qSOFA <2. CONCLUSION: In ED patients with suspected infection, a qSOFA ≥2 was associated with more intensive treatment. This could lead to inadequate prediction of 30-day mortality due to the presence of a treatment paradox. TRIAL REGISTRATION NUMBER: 6916.