Background: Approximately 20% of patients with GERD do not respond to medical therapy. The Stretta radiofrequency antireflux procedure represents an alternative to failed drug therapy for GERD. Objective: The aim of this study was to assess symptom and medication changes after the Stretta procedure during a 4-year follow-up period. Design: Prospective case series on intent-to-treat basis. Setting: Community practice. Patients: Patients with GERD with persistent symptoms despite twice-daily proton pump inhibitor (PPI) medications. Interventions: The Stretta procedure was performed in drug-refractory patients with GERD diagnosed by the presence of endoscopically evidenced esophagitis or abnormal esophageal pH testing. Symptom assessment was performed with a validated health-related quality-of-life questionnaire (with and without medication) at baseline and 6, 12, 24, 36, and 48 months after treatment. Complications of the procedure and medication usage were analyzed. Main Outcome Measurements: Significant changes in symptom scores, GERD quality-of-life parameters, and medication usage on the basis of clinical outcomes. Results: We report on a series of 109 consecutive patients treated with the Stretta procedure who have reached 4-year follow-up. Complete long-term follow-up assessment was available in matched data for 109 patients at 12 months, 108 patients at 24 months, 102 patients at 36 months, and 96 patients at 48 months. A second procedure was performed in 13 patients. Heartburn scores decreased from 3.6 to 1.18 (P < .001), total heartburn score (GERD health-related quality-of-life questionnaire) decreased from 27.8 to 7.1 (P < .001), and patient satisfaction improved from 1.4 to 3.8 (P < .001) (see Table 2). Medication usage decreased significantly from 100% of patients on twice-daily PPI therapy at baseline to 75% of patients showing elimination of medications or only as-needed use of antacids/over-the-counter PPIs at 48 months (P < 0.005). There were no serious complications of the procedure. Limitations: This is an uncontrolled, nonrandomized case series in consecutive patients that does not include long-term pH or motility studies. Conclusions: This study in drug-refractory patients with GERD found the Stretta procedure to be a safe, effective, and durable treatment that produced significant improvements in heartburn and quality of life and decreased medication usage during a 4-year period of follow-up.