OBJECTIVE To compare the efficacy and side effects of low-dose amitriptyline (AMT) with proton pump inhibitor treatment in patients with globus pharyngeus. METHODS Thirty-four patients who fulfilled the Rome III criteria for functional esophageal disorders were included in this study. Patients were randomly assigned to receive either 25 mg AMT before bedtime (AMT group) or 40 mg Pantoprazole once daily for 4 wk (conventional group). The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale (GETS). The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey [social functioning (SF)-36] and the Pittsburgh Sleep Quality Index. Treatment response was defined as a > 50% reduction in GETS scores. All patients entering this study recorded side effects at days 1, 8, 15, 22 and 29 using a visual analogue scale. RESULTS Thirty patients completed the study. After 4 wk of treatment, the AMT group had a greater response than the conventional group (75% vs 35.7%, P = 0.004). At day 3, the AMT group showed significantly more improvement than the Conventional group in GETS score (3.69 ± 1.14 vs 5.64 ± 1.28, P = 0.000). After 4 wk of treatment, the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group (1.25 ± 1.84 vs 3.79 ± 2.33, 4.19 ± 2.07 vs 8.5 ± 4.97; P < 0.01 for both). Additionally, the AMT group was more likely than the Conventional group to experience improvement in the SF-36, including general health, vitality, social functioning and mental health (P = 0.044, 0.024, 0.049 and 0.005). Dry mouth, sleepiness, dizziness and constipation were the most common side effects. CONCLUSIONS Low-dose AMT is well tolerated and can significantly improve patient symptoms, sleep and quality of life. Thus, low-dose AMT may be an effective treatment for globus pharyngeus.