For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1-L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1-L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1-L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1-L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.