OBJECTIVE: To identify distinct developmental patterns of diabetic retinopathy (DR) and assess the risk factor levels of patients in these clusters. RESEARCH DESIGN AND METHODS: A cohort of 3,343 patients with type 2 diabetes mellitus (T2DM) monitored and treated in the Diabetes Care System West-Friesland, the Netherlands, was followed from 2 to 6 years. Risk factors were measured, and two-field fundus photographs were taken annually and graded according to the EURODIAB study group. Latent class growth modeling was used to identify distinct developmental patterns of DR over time. RESULTS: Five clusters of patients with distinct developmental patterns of DR were identified: A, patients without any signs of DR (88.9%); B, patients with a slow regression from minimal background to no DR (4.9%); C, patients with a slow progression from minimal background to moderate nonproliferative DR (4.0%); D, patients with a fast progression from minimal or moderate nonproliferative to (pre)proliferative or treated DR (1.4%); and E, patients with persistent proliferative DR (0.8%). Patients in clusters A and B were characterized by lower risk factor levels, such as diabetes duration, HbA(1c), and systolic blood pressure compared with patients in progressive clusters (C-E). CONCLUSIONS: Clusters of patients with T2DM with markedly different patterns of DR development were identified, including a cluster with regression of DR. These clusters enable a more detailed examination of the influence of various risk factors on DR.