Early detection of latent autoimmune diabetes in adults (LADA) is important in that the earlier insulin therapy is initiated, the greater the preservation of pancreatic beta cells. This study assessed whether a random C-peptide level is an effective screening test for LADA. Random C-peptide levels were measured in 39 subjects with LADA and 39 subjects with type 2 diabetes who were matched for age, race, gender, and duration of diabetes. LADA was definitively diagnosed by the presence of antiglutamic acid decarboxylase antibodies. The mean C-peptide level in the LADA group was 1.0 ± 0.2 ng/mL and 5.1 ± 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.