Background and Objectives: The prevalence of GERD is increasing among individuals with obesity, and RYGB is an effective procedure to control GERD and obesity. However, some patients continue to have GERD after RYGB. The aim of this study was to investigate the prevalence and the risk factors for GERD after RYGB. Material and Methods: This prospective study included 180 RYGB patients followed for an average of 12.2 (0.6) years. In total, 126 (70%) patients agreed to participate and provided data on their weight, GERD symptoms, and filled the GERD-HRQL, TFEQ-18, and GSRS questionnaires. Results: The average age before surgery was 42.7 (10.5) years, and BMI was 45.2 (6.4) kg/m2. Moreover, 128 (71.1%) were females, and preoperative GERD was diagnosed in 74 (41.1%) patients. At the 12-year follow-up, the mean %EBMIL and %TWL was 60.37 and 25.73, respectively. The median %WR was 18.0 (39.0). Postoperative GERD was present in 30 (23.8%) patients, of whom 12 (40%) continued to have GERD symptoms and 18 (60%) developed de novo GERD. The GERD-HRQL score significantly decreased from 3.0 (9.0) at baseline to 2.0 (5.0) (p = 0.028) at 12 years. GSRS Diarrhea and Indigestion scores increased significantly from 1.33 (0.67) to 1.5 (2.42) (p < 0.001) and from 2.0 (1.25) to 2.25 (1.25) (p < 0.001), respectively. No change in the cognitive restraint score was observed. Uncontrolled eating and emotional eating scores decreased from 51.85 (22.22) to 40.74 (33.33) (p < 0.001) and from 44.44 (44.44) to 33.33 (22.22) (p < 0.001), respectively. In the multivariate analysis, %WR > 11 (OR = 3.22, p = 0.029) and GSRS Diarrhea score (OR = 3.21, p = 0.027) were significant predictors of GERD 12 years after RYGB. Conclusions: RYGB was an effective procedure to control GERD; however, 23.8% had persistent or de novo GERD after 12 years. The independent risk factors associated with GERD after RYGB were weight regain and GSRS Diarrhea score.