The anthelmintic efficacy of an aqueous crude extract of the leaves of Vernonia amygdalina Del. (Compositae) was studied in 16 Nigerian puppies. They were divided into four groups of four puppies per group. The group A animals were uninfected and hence were untreated, whereas those in groups B, C, and D were naturally infected with helminths. Group B animals were untreated whereas group C animals were treated with a proprietary anthelmintic (Mebendazole). Group D animals were treated with aqueous crude extracts of V. amygdalina using the oral route. Two weeks after treatment, blood and fecal samples were collected to evaluate the hematologic values and fecal egg counts, respectively. Before the onset of this study, fecal egg counts showed that ascarids (Toxocara canis) and hookworm (Ancylostoma caninum) were present in the experimental animals. The results of this study showed that the aqueous crude extracts of V. amygdalina after its administration into local dogs produced significant changes (p < 0.05) in PCV, RBC, Hb concentration, and TWBC. The fecal egg counts also showed remarkable and significant reduction in the levels of the identified helminths. The effects of the plant extracts were broad spectrum in action. Because the aqueous crude extract of V. amygdalina significantly reduced the fecal egg count of the helminths, it could be a potential source of a new lead anthelmintic agent.