The study examined the economic analysis of sesame production compliant withagricultural restructuring plan in rural areas of Vietnamese Mekong Delta. Conditional non-probability sampling technique was employed to select 90 respondents who have produced sesame rotationally on rice field in summer-autumn crop season. Primary data were analyzed using both descriptive and inferential statistics including percentage, frequency and farm budget model. Gross Margin analysis was used to estimate cost, returns sesame production in the study area. The study revealed that the average cost, revenue, gross margins of production per hectare was 17.60, 37.38 and 20.56 million VND, respectively.Moreover,the average rate of returnsalsoindicated that with every 1,000 VND invested to sesame production, a farmer made a profit of 1,390 VND. As a result, it can be concluded that sesame farming is profitable in the context of agricultural restructuring strategy from rice to other crops in Mekong Delta region. It is recommended that smallholders should take initiative in participation in sesame cooperatives and ‘big field' model to be more beneficial to inputs price, harvested machine and formal credit in the beginning of each season.