The impact of right bundle branch block (RBBB) on exercise ECG for the diagnosis of coronary artery disease is not well defined. Therefore, the diagnostic accuracy of ST segment deviation during exercise ECG was compared to perfusion scintigraphy in 88 patients with RBBB. A positive study for exercise ECG was defined as 1 mm ST segment deviation from baseline in two contiguous leads while a reversible perfusion defect was defined as a positive scintigraphic result. Overall test specificity was 48% while sensitivity was 85%. When ECG changes in regional leads were considered, inferior leads (II, III, aVf) and lateral leads (V4, V5, V6) showed similar specificity and sensitivity 93% and 94%, and 29% and 50%, respectively. Anterior lead changes(V1, V2, V3) demonstrated a decline in specificity 51% with a sensitivity of 85%. Exercise ST deviation in the setting of known resting ST-T abnormalities of any cause have a known poor specificity for the diagnosis of coronary artery disease. A similar impact was seen on the exercise ECG in RBBB. In leads in which resting ST-T wave abnormalities due to RBBB were present, the specificity of exercise ST changes was reduced to 53%. In leads without ST-T abnormalities specificity was 92%. Most false positives occurred in the anterior leads. We compared tests where resting ST-T abnormalities occurring in V1 only (V1 group), to those with changes in V1, and V2, and/or V3 (V1-3 group). The V1 group showed a specificity of 61% and a sensitivity of 100% while the V1-3 group demonstrated a decline in both specificity and sensitivity to 41% and 75%, respectively. Thus, in patients with RBBB, sensitivity of the exercise ECG is similar to patients with normal ECGs. Specificity is also similar to normal ECGs if the inferior, lateral precordial and anterior precordial leads with abnormalities in V1 only are considered.