Purpose To create and validate a computer system with which to detect, localize, and classify compression fractures and measure bone density of thoracic and lumbar vertebral bodies on computed tomographic (CT) images. Materials and Methods Institutional review board approval was obtained, and informed consent was waived in this HIPAA-compliant retrospective study. A CT study set of 150 patients (mean age, 73 years; age range, 55-96 years; 92 women, 58 men) with (n = 75) and without (n = 75) compression fractures was assembled. All case patients were age and sex matched with control subjects. A total of 210 thoracic and lumbar vertebrae showed compression fractures and were electronically marked and classified by a radiologist. Prototype fully automated spinal segmentation and fracture detection software were then used to analyze the study set. System performance was evaluated with free-response receiver operating characteristic analysis. Results Sensitivity for detection or localization of compression fractures was 95.7% (201 of 210; 95% confidence interval [CI]: 87.0%, 98.9%), with a false-positive rate of 0.29 per patient. Additionally, sensitivity was 98.7% and specificity was 77.3% at case-based receiver operating characteristic curve analysis. Accuracy for classification by Genant type (anterior, middle, or posterior height loss) was 0.95 (107 of 113; 95% CI: 0.89, 0.98), with weighted κ of 0.90 (95% CI: 0.81, 0.99). Accuracy for categorization by Genant height loss grade was 0.68 (77 of 113; 95% CI: 0.59, 0.76), with a weighted κ of 0.59 (95% CI: 0.47, 0.71). The average bone attenuation for T12-L4 vertebrae was 146 HU ± 29 (standard deviation) in case patients and 173 HU ± 42 in control patients; this difference was statistically significant (P < .001). Conclusion An automated machine learning computer system was created to detect, anatomically localize, and categorize vertebral compression fractures at high sensitivity and with a low false-positive rate, as well as to calculate vertebral bone density, on CT images. © RSNA, 2017 Online supplemental material is available for this article.