INTRODUCTION: Esophageal hypersensitivity is associated with gastroesophageal reflux disease (GERD). Since sleep disturbance causes esophageal hypersensitivity, hypnotics may ameliorate GERD. However, zolpidem prolongs esophageal acid clearance. Lemborexant is a new hypnotic with higher efficacy and fewer adverse events than zolpidem. Therefore, the present study investigated the effects of lemborexant on GERD. METHODS: Patients with heartburn and/or regurgitation and insomnia who did not take acid suppressants or hypnotics in the last month were recruited. Symptom assessments using GerdQ and reflux monitoring were performed before and after a 28-day treatment with 5 mg lemborexant at bedtime. The primary outcome was a change in the total GerdQ score, excluding the score for insomnia. Secondary outcomes were changes in each GerdQ score and the following parameters on reflux monitoring: the acid exposure time (AET), number of reflux events (RE), acid clearance time (ACT), and post-reflux swallow-induced peristaltic wave (PSPW) index. RESULTS: Sixteen patients (age 45.0 [33.3-56.0], 11 females [68.8%]) completed the intervention (1 patient did not tolerate the second reflux monitoring). The total GerdQ score, excluding the score for insomnia, did not significantly change (8.0 [6.0-9.0] before vs. 7.0 [6.3-9.0] after p = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0-3.0] vs. 1.0 [0-2.8] p = 0.0054) but not heartburn (2.5 [1.0-3.0] vs. 1.0 [0.3-2.0] p = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention. CONCLUSION: Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.