To study the value of high enhanced serosa sign on contrast-enhanced computed tomography (CT) in differentiating T3 from T4a gastric cancer in different Lauren classification. This study included 276 consecutive patients with surgically confirmed pT3 or pT4a gastric cancers. The pre-operative CT images were reviewed by two radiologists blinded. The demonstration of the high enhanced serosa on CT between T3 and T4a was compared with chi-square test. The diagnostic performance of this sign on CT in the differentiation of T4a from T3 in different Lauren classification was calculated. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the judgement of serosa invasion using the high enhanced serosa sign on CT was 74.6%, 63.7%, 83.6%, 76.0% and 73.8% by one radiologist and 76.4%, 66.1%, 84.9%, 78.1% and 75.4% by the other radiologist. Compared to the intestinal-type, the sensitivity of the judgement of serosa invasion using the high enhanced serosa sign on CT in diffuse-type was significant higher (80% in both readers), while the specificity trended to be lower (65.9% and 80.5%, respectively). There is no significant difference in the accuracy of diagnosis between intestinal-type and diffuse-type of gastric cancers (the P-values of two radiologists were 0.968, 0.591, respectively). The combination of the high enhanced serosa sign with conventional CT signs is significant different in diagnosis of T3 and T4a (P<0.001). The diagnostic accuracy was increased in both radiologists after the combination. The two readers achieved substantial agreement, with Kappa coefficient of 0.63, P<0.001. The high enhanced serosa sign on CT is associated with serosa involvement. The sensitivity of the judgement of serosa invasion using this sign on CT in diffuse-type was significant higher than that in intestinal-type.