Reflux of contrast medium into the inferior vena cava (IVC) is often detected on computerized tomographic pulmonary angiogram. The potential clinical implications and associated diagnoses of this finding have not been established. We investigated the prevalence and significance of reflux of contrast medium into the IVC in a large cohort of patients evaluated for possible pulmonary embolism (PE) by computerized tomographic pulmonary angiography. We retrospectively reviewed 1,065 consecutive computerized tomographic pulmonary angiographic examinations performed from January 1, 2007 through January 7, 2008 for the presence of reflux. Degree of reflux into the IVC and hepatic veins was graded from 1 (none) to 6 (severe). Patients' charts were reviewed for diagnoses during the index hospitalization and for background diseases. These clinical data were correlated with the reflux grade. The final study included 967 computerized tomographic pulmonary angiographic scans of 367 men and 600 women (mean age 62 ± 20 years, range 17 to 103). Almost 1/2 (480, 49.6%) had grade 1, 310 (32.1%) had grades 2 to 3, and 177 (18.3%) had grades 4 to 6. Multivariate logistic regression found that pulmonary hypertension, history of congestive heart failure, chronic atrial fibrillation, and acute PE were associated with extensive reflux (grades 4 to 6) with odds ratios (95% confidence intervals) of 5.4 (3.0 to 9.9, p <0.001), 3.7 (2.3 to 6.1, p <0.001), 2.3 (1.0 to 5.3, p = 0.044), and 1.8 (1.2 to 2.9, p = 0.011), respectively. Interobserver agreement between the 2 readers for reflux grading was good (kappa = 0.77). In conclusion, extensive reflux of contrast medium into the IVC detected on computerized tomographic pulmonary angiogram may serve as a pathophysiologic marker of right heart dysfunction, specifically pulmonary hypertension, congestive heart failure, chronic atrial fibrillation, or PE.