Herein, we present a facile and comprehensive synthetic methodology for the preparation of polyester-polyamidoamine (PAMAM) (i.e., polyester: polylactide [PLA] (hydrophobic) and polyamidoamine, PAMAM [hydrophilic]) polymers. A library of PLA-PAMAM linear dendritic block copolymers (LDBCs) in which both l and d, l polylactide were employed in mass ratios of 30:70, 50:50, 70:30, and 90:10 (PLA:PAMAM) were synthesized and analyzed. When placed in aqueous media, the immiscibility of the hydrophilic and hydrophobic segments leads to nanophase-segregation exhibited as the formation of aggregates (e.g., vesicles, worms, and/or micelles). By employing both stereochemical configurations of PLA, the differentiation in mass ratios of PLA-PAMAM aided in elucidating the structure-property relationships of the LDBC system and provided a means toward the control of nanoparticle morphology. Transmission electron microscopy and dynamic light scattering afford the size and shape of the nanoparticles with diameters ranging from 10.6 for low mass ratios to 122.4 nm for high mass ratios of PLA-PAMAM and positive zeta-potential values between +24.7 mV and +48.2 mV. Furthermore, small-angle X-ray scattering (SAXS) studies were employed to obtain more detailed information on the morphological assemblies constructed via direct dissolution. Such insights provide a pathway toward nanomaterials with unique morphologies and tunable properties deemed relevant in the development of next generation biomaterials. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1448-1459