Background Neuromodulators are considered potential therapeutic options for refractory gastro-oesophageal reflux-induced chronic cough. Aim To compare the efficacy of gabapentin and baclofen in patients with suspected refractory gastro-oesophageal reflux-induced chronic cough. Methods Two hundred and thirty-four patients with suspected refractory gastro-oesophageal reflux-induced chronic cough, who failed an 8-week course of omeprazole and domperidone, were recruited into the open-labelled study and randomly assigned to receive either gabapentin (maximum daily dose of 900 mg) or baclofen (maximum daily dose of 60 mg) for 8 weeks as add-on therapy to the previous treatment. The primary end point was the successful rate of cough resolution; and the secondary end-points included cough sensitivity to capsaicin and gastro-oesophageal reflux disease questionnaire score and reported side effects. Results One hundred and eleven patients in the gabapentin group and 106 in the baclofen group completed the study. The overall success rate for cough resolution was comparable (57.3% vs 53.0%, chi(2) = 0.357, P = 0.550) between the two groups. In parallel, cough sensitivity to capsaicin and gastro-oesophageal reflux disease questionnaire score decreased after treatment with either gabapentin or baclofen. However, gabapentin was associated with less frequent somnolence (20.5% vs 35.0%, chi(2) = 6.156, P = 0.013) and dizziness (11.1% vs 23.9%, chi(2) = 6.654, P = 0.010) than baclofen. Conclusions Gabapentin and baclofen have similar therapeutic efficacy for suspected refractory gastro-oesophageal reflux-induced chronic cough. However, gabapentin may be preferable because of fewer side effects. Trial Register: ; No.: ChiCTR-ONC-13003066.