Autonomic nervous system (ANS) is governed by complex interactions arising from feedback loops of nonlinear systems that operate over a wide range of temporal and spatial scales, enabling the organism to adapt to stress, metabolic changes and diseases. This study is aimed to assess multifractal and nonlinear characteristics of the ANS during ischemic events provoked by a prolonged percutaneous coronary intervention (PCI) procedure. Eighty-seven patients from the STAFF III database were used. Patients were classified into 2 groups: (1) with prior myocardial infarction (MI) and (2) without MI (noMI). R-R signals during three 3-min stages of the procedures were analyzed using multifractal and surrogate data techniques. Multifractal indices increased significantly from the pre-inflation stage to the post-deflation stage. These variations were more marked for the noMI group. Multifractal changes significantly correlated with both the decreased parasympathetic and the increased sympathetic modulations accounted by classical linear indices. Multifractal measures resulted to be a more powerful indicator than linear HRV indices in quantifying the ischemia-induced changes. Right coronary artery (RCA) occlusions provoke greater multifractal reactions throughout the PCI procedure. Our findings suggest reduced complex multifractal and nonlinear reactions of ANS activity in patients with prior MI in comparison to the noMI group, possibly due to degradation in the complexity of control mechanism of heart rate generation.