Background and Purpose This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) on sleep-disordered breathing (SDB), daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy (DRE). It also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. Methods Twenty-four patients were recruited. Paired t -tests and multiple linear regression analyses were performed to determine how the demographic and clinical characteristics of the patients influenced the variables that changed significantly after VNS treatment. Results After VNS, the patients showed significant increases in the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), apnea index, hypopnea index, and oxygen desaturation index (ODI), as well as a significant decrease in the lowest arterial oxygen saturation (SaO 2 nadir) ( p <0.05). The multiple linear regression analyses demonstrated that the predictor of larger increases in AHI and RDI was being older at baseline, and that the predictor of a larger increase in apnea index was a longer epilepsy duration. The strongest predictor of a larger increase in ODI was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. The strongest predictor of a larger decrease in SaO 2 nadir was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. Conclusions This study has confirmed that VNS improves seizure control in patients with DRE, whereas it increases obstructive sleep apnea (OSA). Furthermore, the increase in OSA is affected by age and the duration of epilepsy. Therefore, careful observation and monitoring of SDB is recommended in patients who undergo VNS.