OBJECTIVES: Gastroesophageal reflux disease (GERD) has substantial impact in primary care, but the optimal approach to management is uncertain. A structured management strategy may improve the diagnosis and therapeutic management of GERD, but individual studies may be limited by their focus on local strategies that may not be valid for other countries. METHODS: We conducted a meta-analysis of five cluster randomised clinical trials comparing a new management strategy with usual care in patients with GERD conducted in Austria, Italy, Norway, Spain and Sweden (NCT00842387). The intervention strategy was based on the self-administered validated GerdQ questionnaire to stratify adult patients with classical symptoms of GERD (heartburn or regurgitation) according to the frequency and impact of symptoms. The most effective acid-suppressive therapy (esomeprazole 40 mg once daily) was used only in patients with the highest GerdQ symptom impact score (≥3). The primary outcome was non-response to treatment defined as a total GerdQ score ≥8 at the end of follow-up. Odds ratios for the primary outcome were combined using a random effects model. RESULTS: A total of 2400 patients were enrolled and average follow-up ranged from 4 to 18 weeks. The odds ratios for lack of treatment response with the structured management strategy compared with usual care ranged from 0.22 to 0.84, across studies. The random-effects combined odds ratio for non-response to treatment was 0.56 (95% CI 0.22 – 0.90; p = 0.001), with significant between-study heterogeneity (p <0.001). CONCLUSIONS: Stratification of patients according to the GerdQ questionnaire, using a locally adapted primary care management strategy for GERD significantly increased the likelihood of a response to treatment compared to usual clinical practice, although significant between-country heterogeneity suggests that GERD management can still be improved.