We investigated the role of right-to-left shunt with standardized transcranial Doppler ultrasonography in a large population of divers referred for symptoms of decompression illness. Case series compared with a control group. Military teaching hospital, hyperbaric unit. Patients were 101 consecutive divers with clinical evidence of decompression illness and a control group of 101 healthy divers. Specification of the type of decompression illness involved and detection/evaluation of right-to-left shunt by standardized transcranial Doppler. The degree of right-to-left shunt was defined as major if the number of high-intensity transient signals in the middle cerebral artery was >20. We evaluated the odds ratios by logistic regression analysis with vs. without right-to-left shunt for subjects with cochleovestibular symptoms, cerebral decompression illness, spinal decompression illness, and Caisson sickness. Of the 101 divers presenting with decompression illness, transcranial Doppler detected a right-to-left shunt in 59 (58.4%), whereas control subjects demonstrated a right-to-left shunt in 25 cases (24.8%; odds ratio, 4.3; 95% confidence interval, 2.3-7.8; p=.09). When a right-to-left shunt was detected, the right-to-left shunt was major in 12 of 25 patients in the control group and in 49 of 59 patients in the decompression illness group (odds ratio, 8.7; 95% confidence interval, 4.2-18.0; p<.001). Within the decompression illness group, the proportion of major right-to-left shunt was 24 of 34 (odds ratio, 29.7; 95% confidence interval, 10.0-87.2; p<.0001) in the cochleovestibular subgroup, 13 of 21 (odds ratio, 24.1, 95% confidence interval, 6.8-86.0, p< 0.0001) in the cerebral decompression illness subgroup, ten of 31 (odds ratio, 3.9; 95% confidence interval, 1.5-10.3; p<.01) in the spinal decompression illness subgroup, and two of two (odds ratio, 1.1; 95% confidence interval, 0.2-5.7; p=.9) in the subgroup of divers with Caisson sickness. Based on our results, we conclude that major right-to-left shunt was associated with an increased incidence of cochleovestibular and cerebral decompression illness, suggesting paradoxical embolism as a potential mechanism.