BACKGROUND Heterobilharzia americana (HA), the causative agent of canine schistosomiasis, is a flatworm with a freshwater snail as an intermediate host. Only case reports or small case series evaluating naturally infected dogs have been published. OBJECTIVE Describe clinical signs in dogs naturally infected with HA. METHODS Twenty-two dogs naturally infected with HA from 1985 to 2009. METHODS Retrospective study. All medical records were searched for HA and schistosomiasis. Only dogs with a diagnosis based on identification of ova on histopathology or fecal saline sedimentation were included. RESULTS The median age was 3.1 years (1-12). The median duration of clinical signs before diagnosis was 0.63 months (0.03-12). The most common clinical signs were lethargy (91%), weight loss (77%), hyporexia (68%), vomiting (59%), and diarrhea (55%). Eleven of the 22 dogs were hypercalcemic. Hypercalcemia did not resolve without definitive treatment with praziquantel. HA infection was an incidental diagnosis in 7/22 dogs. Diagnosis was obtained via necropsy (4), histopathology (9), and fecal examination (9). Definitive treatment included praziquantel and fenbendazole. Eighteen dogs were diagnosed antemortem and 17 were treated. Twelve dogs were alive for 6 months to 3 years after diagnosis. CONCLUSIONS HA infection occurs in younger, larger breed, indoor dogs. Hypercalcemia does not resolve without praziquantel treatment. Prognosis is good and neither hypercalcemic-induced renal failure nor ascites appears to worsen prognosis. Dogs in affected areas or that have traveled to affected areas that present for weight loss, gastrointestinal or liver disease, and hypercalcemia, should be tested.