Background/Objectives: Chronic nausea and vomiting (N/V) disorders are common in clinical practice. Our primary aim was to compare total and segmental gastrointestinal transit times as well as gastric contraction patterns in patients with chronic N/V syndrome to those of healthy volunteers (HVs). In the patient group, our secondary aim was to explore how symptoms and motility patterns were affected by a serotonin HT₄ receptor agonist (Prucalopride). Methods: Patients with chronic N/V syndrome and HVs underwent baseline assessment of regional gastrointestinal (GI) motility/transit using the Motilis 3D-Transit system. Patients were then treated with Prucalopride 2 mg daily for 28 days, with the 3D-transit examination repeated within 10–20 days after treatment onset. Two self-administered questionnaires (the Gastrointestinal Symptom Rating Scale [GSRS] and Gastroparesis Cardinal Symptom Index [GCSI]) were used to assess patients’ symptoms. Results: A total of 19 patients (13 F; median age 25 years (IQR 22–39) and 55 HVs (25 F; median age 28 (24–35) were included. At baseline, no differences in regional GI transit times were found between groups. However, patients had a significantly lower gastric contraction amplitude than HVs (9 mmHg (IQR 8–11) vs. 12 (10–15: p < 0.001). In response to Prucalopride treatment, gastric emptying time was reduced from a median of 3.1 h to 1.6 h (p < 0.005). Further, the GCSI was significantly reduced from GCSI 3.0 (IQR 2.3–3.7) at baseline to GCSI 1.9 (IQR 1.3–3.2) with Prucalopride. Conclusions: Patients with chronic N/V syndrome have significantly lower gastric contraction amplitude than HVs and may symptomatically benefit from prokinetics. They do not, however, have evidence of panenteric dysmotility.