Proton pump inhibitor (PPI) twice daily dosing is a standard therapy for gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) but there is no data on its response rate or the predictors of PPI-partial response GERD. Aims were to determine the prevalence of PPI-partial response GERD in SSc and to define its predictors. A prospective study was conducted in SSc patients with GERD. The patients were treated with omeprazole 20 mg bid for 4 weeks. The severity of symptom-grading by visual analogue scale (VAS) and frequency of symptoms by frequency scale for symptoms of GERD (FSSG) were assessed at baseline and 4 weeks after treatment. PPI-partial response GERD was defined as less than 50% improvement in the VAS for severity of symptom as well as acid reflux score by FSSG after treatment. According to the sample size calculation, 243 SSc-GERD patients were enrolled; of whom 166 (68.3%) had the diffuse cutaneous SSc. PPI-partial response GERD was found in 131 SSc patients (prevalence 53.9%; 95%CI 47.4-60.3). The multivariate analysis revealed that esophageal dysphagia was an only predictor the PPI-partial response GERD (OR 1.82; 95%CI 1.01-3.29) while neither SSc subset nor severity of skin tightness were significantly associated with PPI-partial response GERD. Half of the SSc patients were PPI-partial response GERD. Esophageal dysphagia was the only predictor of PPI-partial response GERD in SSc patients. Screening for dysphagia before starting GERD treatment is helpful for assessment the risk of PPI refractoriness GERD in SSc patients.