To compare the diagnosis of diabetic macular edema (DME) by stereoscopic slit-lamp biomicroscopic examination of the fundus with a 78-diopter noncontact lens with diagnosis by optical coherence tomography (OCT). Prospective, double-masked, noninterventional diagnostic study. Analysis of slit-lamp biomicroscopic findings compared with OCT measurements. Patients with DME from a private retina practice. Presence or absence of macular thickening. The reference range for this clinic was comparable to reference ranges published from other clinics. The clinical detection of DME was less than detection by OCT. Chance-corrected agreements (kappa statistic) of the 2 methods were 0.63 for the foveal zone and 0.36 to 0.42 for the 4 parafoveal zones. The errors committed in clinical examination were primarily of the type in which clinical examination did not detect DME but OCT did (58%-90%) for the 5 zones analyzed. Reference ranges for OCT seem to be similar for different clinical settings, suggesting the usefulness of OCT in multicenter studies. The current standard of care for DME detection, stereoscopic slit-lamp examination of the fundus, is less sensitive than OCT for detection of DME. Because the principal therapy for DME, focal laser photocoagulation, is mainly sight preserving and not sight restoring, the wider use of OCT may beneficially impact visual disability from DME.