Background <p>There is reason to believe that unfavorable outcomes of non-ST-elevation acute coronary syndrome (NSTE-ACS) is due to the “risk-treatment” paradox (RTP). However, the true prevalence, types and causes of RTP have not been studied, and data from previous studies have shown an equivocal effect of RTP on outcomes of NSTE-ACS.</p> Methods <p>The retrospective analysis included 600 patients initially diagnosed with NSTE-ACS. Upon admission, all patients were re-stratified into four groups according to their risk of adverse ischemic events. RTP was defined as a mismatch between a patient’s risk profile and the recommended invasive strategy.</p> Results <p>RTP was present in 53.5% of the study population (321/600), with the highest frequency observed in the intermediate-risk group (74%) and the lowest in the high-risk group (28.5%). In the overall cohort, the presence of RTP (<i>n</i> = 321) was not associated with a significant difference in in-hospital adverse cardiovascular events or length of stay compared to patients without RTP (<i>n</i> = 279). After adjustment for RTP in each risk group, only the high-risk group showed an increase in adverse outcomes in the presence of RTP (5.4% mortality vs. 2.9% (OR 1.9 (95% CI 0.5–8.9), <i>p</i> = 0.037) and a negative effect of RTP on the risk of recurrent myocardial ischemia (RMI) after 24&#xa0;h (7.1% vs. 0.7%, OR 10.7 (95% CI 1.2–97.9), <i>p</i> = 0.01).</p> Conclusions <p>RTP in relation to the type of invasive strategy is common in patients with NSTE-ACS (53.5%). For high-risk patients, RTP worsened in-hospital outcome and influenced the risk of RMI after 24&#xa0;h.</p> Clinical trial number <p>This research is a retrospective observational study, which does not require mandatory registration as defined by the ICMJE.</p>