Background & Aims: Functional dyspepsia (FD) is considered a heterogeneous disorder with different pathophysiological mechanisms contributing to the symptom pattern. The Rome II committee proposed that subdividing patients with FD into groups with predominant pain versus discomfort might identify subgroups with homogeneous pathophysiological and clinical properties. The aim of this study was to analyze the relationship of predominant pain or discomfort with pathophysiological mechanisms and to evaluate whether considering individual predominant symptoms yields better results. Methods: Consecutive FD patients (n = 720; 489 women; mean age, 41.3 ± 0.6 years) filled out a dyspepsia questionnaire and identified a single most bothersome symptom. We analyzed the association of this predominant symptom with demographic, clinical, and pathophysiological features (Helicobacter pylori status, gastric emptying in 592 patients, and gastric sensitivity and accommodation testing in 332 patients). Results: According to Rome II criteria, 22% were pain predominant and 78% discomfort predominant. Patients with predominant pain had a higher prevalence of hypersensitivity (44% vs 25% ) and delayed gastric emptying was observed less frequently in these patients (16% vs 26% ), but there was major overlap. Detailed analysis showed that any of 8 dyspeptic symptoms could be predominant. Predominant early satiety or vomiting was associated with significantly higher prevalences of weight loss (89% and 75% , respectively) and of acute onset (61% and 60% , respectively). Impaired accommodation was found in 79% of patients with predominant early satiety. The highest prevalence of delayed emptying was found in predominant fullness (38% ) and of hypersensitivity in predominant pain (44% ). Conclusions: Subdividing FD patient groups according to the predominant symptom does not reliably identify subgroups with a homogeneous underlying pathophysiological mechanism. Background & Aims: Functional dyspepsia (FD) is considered a heterogeneous disorder with different pathophysiological mechanisms contributing to the symptom pattern. The Rome II committee proposed that subdividing patients with FD into groups with predominant pain versus discomfort might identify subgroups with homogeneous pathophysiological and clinical properties . The aim of this study was to analyze the relationship of predominant pain or discomfort with pathophysiological mechanisms and to evaluate whether invest individual predominant symptoms yields better results. Methods: Consecutive FD patients (n = 720; 489 women; mean age, 41.3 ± 0.6 years) filled out a dyspepsia questionnaire and identified a single most bothersome symptom. We analyzed the association of this predominant symptom with demographic, clinical, and pathophysiological features (Helicobacter pylori status, gastric emptying in 592 patients, and gastric sensitivity and accommodation testing in 332 R 22% were pain predominant and 78% discomfort predominant. Patients with predominant pain had a higher prevalence of hypersensitivity (44% vs 25%) and delayed gastric emptying was observed less frequently in these patients (16% Detailed analysis showed that any of 8 dyspeptic symptoms could be predominant. Predominant early satiety or vomiting was associated with significantly higher prevalences of weight loss (89% and 75%, respectively) and of of acute Impaired accommodation was found in 79% of patients with predominant early satiety. The highest prevalence of delayed emptying was found in predominant fullness (38%) and of hypersensitivity in predominant pain (44%). Conclusions: Subdividing FD patient groups according to the predominant symptom does not reliably identify subgroups with a similar underlying pathophysiological mechanism.