Internet gaming disorder (IGD), defined as an inability to control Internet-based game play, leads to serious impairment in psychological and social functioning, but few studies have identified the neurophysiological characteristics of patients with IGD. The aim of this study was to determine neurophysiological markers of P300 components associated with changes in symptoms after outpatient management with pharmacotherapy in patients with IGD. The present prospective longitudinal study included 18 patients with IGD and 29 healthy controls. The patients with IGD completed a 6-month outpatient management program including selective serotonin reuptake inhibitor-based pharmacotherapy. Event-related potentials (ERPs) were acquired during the auditory oddball task. ERPs of the patients with IGD were recorded before and after treatment. Between-group differences and the pre-to-post treatment differences in P300 components were investigated using repeated-measures analysis of variance. The primary treatment outcome was a change in score on Young Internet Addiction Test between before and after treatment. At baseline assessments, the IGD group showed significantly reduced P300 amplitudes and delayed latencies at the midline centro-parietal site compared with those in the healthy controls. No significant changes in the P300 indices were observed between pre and post-treatment in the patients with IGD after 6 months of treatment, even though the patients with IGD exhibited significant improvements in their IGD symptoms. Furthermore, no significant difference in ERPs was observed between responders and nonresponders to a 6-month treatment in patients with IGD. These results suggest that reduced P300 amplitudes and delayed latencies are candidate endophenotypes in the pathophysiology of IGD.