Antitumor and antiangiogenic active dendritic compounds conjugated with 5-fluorouracil (5-FU) were synthesized and characterized. First, the core structure based on ascorbic acid and dicarboxylic acid was synthesized, amidated with ethylenediamine. For the synthesis of higher generated dendrimer, it was reacted further with methyl acrylate to increase molecular weight through Michael addition reaction, followed by the continuous repeating amidation reaction, finally, used to synthesize covalently bound dendrimer/5-FU conjugates. The in vitro cytotoxicities of the conjugates was evaluated with mouse mammary carcinoma, mouse leukemia, and human histiocytic lymphoma as cancer cell lines and mouse liver cells as a normal cell line, and showed lower values than 5-FU. The in vivo antitumor activities of the conjugates against mice bearing sarcoma 180 tumor cell line were better than 5-FU. Especially, Second generated dendrimer (G-2)/5-FU conjugates showed excellent in vivo antitumor as well as antiangiogenic activities evaluated by the embryo chorioallantoic membrane assay due to slow hydrolysis rate and the amount of 5-FU released. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.