Background Medical, endoscopic, and open/laparoscopic surgical methods are used to treat gastroesophageal reflux disease (GERD). This study aimed to perform a systematic review of randomized controlled trials comparing medical and surgical treatments of GERD in adult patients. Methods For the study, MEDLINE and EMBASE (1980-2012) were searched. Two reviewers independently assessed methodologic aspects and extracted data from eligible studies, focusing on patient-relevant outcomes. The primary outcomes were health-related and GERDspecific quality-of-life aspects. Standardized mean differences (SMDs) between treatment groups were calculated and combined using random-effect meta-analysis. Results The study identified 11 publications reporting on 7 trials comparing surgical (open or laparoscopic) and medical treatment of GERD. Meta-analysis of both qualityof- life aspects showed a pooled-effect estimate in favor of fundoplication (SMD 0.18; 95 % confidence interval [CI] 0.01-0.35; SMD 0.33; 95 % CI 0.13-0.54). Heartburn and regurgitation were less frequent after surgical intervention. However, a considerable proportion of patients still needed antireflux medication after fundoplication. Nevertheless, the surgical patients were significantly more satisfied with their symptom control and showed higher satisfaction with the treatment received. Conclusions This systematic review showed that surgical management of GERD is more effective than medical management with respect to patient-relevant outcomes in the short and medium term. However, long-term studies still are needed to determine whether antireflux surgery is an equivalent alternative to lifelong medical treatment.