Background: Roux-en-y gastric bypass (RYGB) surgery produces significant weight loss, however a number of patients experience some and/or complete recidivism of weight years after surgery. Limited research has investigated why patients are experiencing weight regain after surgical interventions. Our objective was to identify appetite-related measures associated with weight regain after RYGB surgery. Methods: Using a cross-sectional design, 29 participants (49.6 ± 9.1 years of age; 29-62 months post-RYGB) were divided into three weight categories; (weight maintainers, n = 9; low weight regainers, n = 10; and high weight regainers, n = 10). Appetite, smell function, eating behaviours and food reward were measured in response to a standardized meal. Results: Weight regain increased significantly in association with time after surgery (rs = 0.768, p = 0.016). High regainers gained on average 8.6 kg/year, compared to low regainers and maintainers, 3.8 ± 0.9 kg/year and 0.9 ± 0.9 kg/year, respectively (p < 0.001). Dietary restraint (using the Three Factor Eating Questionnaire) was significantly higher in weight maintainers and low regainers compared to high regainers using clinical subscales (p < 0.05). Weight regain was associated with higher “liking” of high-fat sweet foods (measured with the Leeds Food Preference Questionnaire) among high weight regainers. Conclusion: Weight regain after RYGB may be associated with higher preferences for high-fat sweet foods, whereas, higher dietary restraint may be associated with lower wanting of high-fat sweet foods among weight maintainers. Findings provide insight into why some patients after RYGB regain weight, while others maintain their weight. Future research is needed to further explore the relationships between appetite-related factors and weight regain after RYGB employing a longitudinal study design.