The current study was organized to measure the economic efficiency of rice-shrimp farms in the Mekong Delta. Thus, a survey on 84 rice-shrimp farmers was conducted in 28 villages of 24 districts in Ca Mau and Kien Giang in the western coastal region of the Mekong Delta. Data were selected using random sampling, and data envelopment analysis was applied to assess the economic efficiency of the rice-shrimp system. The overall average for technical efficiency (TE) and scale efficiency (SE) were 0.665 and 0.509, respectively, implying substantial inefficiency in farming operations by the households in the sample. This indicates that there is still potential for improving the economic efficiency of the rice-shrimp system. In addition, the land ownership status, the area cultivated, and the type of seed are statistically significant determinants of the TE while factors of gender, age, education level, irrigation system, saltwater drains, area, type of seed, and practices of fertilizing and weeding are the determinants of the SE. Based on the data recorded it was confirmed that farms in Kien Giang attain higher economic profit, TE, and SE than farms in Ca Mau.