To explore the value of cough maneuver (CM) in detecting right-to-left (RLS) during contrast transthoracic echocardiography (cTTE) and its mechanism. We enrolled 196 patients with a high level of clinical suspicion of RLS underwent cTTE for RLS detection. Valsalva maneuver (VM) (blowing into a face mask connected to a sphygmomanometer at 40 mm Hg for 10 seconds) and CM were performed to provoke RLS, respectively. A comparison of the two provocative maneuvers in terms of the RLS-detection rate, the degree of RLS, the mobility of septum primum was done. The detection rates of RLS for CM were significantly higher than that for VM (38.3% vs 32.1%), (P < 0.001). There was no significant difference between VM and CM in terms of detecting moderate- or severe-extent RLS (P > 0.05), however, CM was significantly better than VM in detecting mild-extent RLS (P = 0.004). CM caused a greater mobility of septum primum than VM (20.1 ± 0.2 mm vs 6.3 ± 0.1 mm), (P < 0.001). Cough maneuver had a higher detection rate for RLS than VM during cTTE, maybe due to its greater mobility of septum primum than VM caused.