Aspartic acid has been developed as a versatile and highly efficient organocatalyst for the three component combination of homophthalic anhydride, aldehydes, and ammonium acetate to afford trans-isoquinolonic acids. The reactions were carried out in acetonitrile under reflux conditions. Aspartic acid as an efficient organocatalyst exhibits dramatically improved diastereoselectivity compared with previously reported catalysts for this synthetic strategy.