Marfan syndrome (MFS) is diagnosed according to the Ghent nosology, which has recently been revised. In the Netherlands, evaluation for possible MFS is performed in specialized Marfan outpatient clinics. We investigated the diagnostic yield in our clinic and the impact of the 2010 nosology. All adult patients (n = 343) who visited our clinic between 1998 and 2008 were included. We analyzed their reasons for referral, characteristics, and established diagnoses. In addition, we applied the 2010 nosology to all patients and compared the outcomes to those obtained with the 1996 nosology. Diagnoses that were made using the 1996 and the 2010 Ghent nosology included MFS (44/343 vs. 47/343), familial thoracic aortic aneurysm and/or dissection (22/343 vs. 22/343 patients), Loeys–Dietz syndrome (4/343 vs. 4/343 patients), and (familial) mitral valve prolapse (MVPS; 5/343 vs. 28/343 patients). In both nosologies, 77% of MFS patients had an FBN1 mutation. The 2010 nosology led to an increase in the number of diagnoses made: 4 additional cases of MFS were identified (one patient was “lost” who no longer fulfilled the criteria) and 23 additional cases of MVPS were diagnosed. The diagnostic yield of patients with aortic root dilatation was 65% using the 1996 nosology and 70% using the 2010 nosology. The change in diagnoses did not lead to a difference in clinical follow-up. We conclude that the diagnostic yield of our specialized clinic was high, in particular in patients with aortic root dilatation. Further more the 2010 Ghent nosology led to a significant increase in the number of diagnoses made, mainly due to lowering of the diagnostic threshold for MVPS. © 2012 Wiley Periodicals, Inc.