For dogs with protein-losing enteropathy (PLE) and evidence of lymphangiectasia, the efficacy of low-fat diet as monotherapy or combined with prednisone remains poorly characterized. In this prospective, observational cohort study of 14 dogs with presumptive PLE and ultrasonographic evidence of lymphangiectasia, subjects were placed on various low-fat diets as monotherapy and prednisone was added if response was deemed inadequate. Dogs were assessed and scored at four recheck examinations across a 6 mo study period, including a final recheck ultrasound. Clinical and clinicopathologic variables were collected and dogs were divided into three outcome groups: clinical remission on dietary monotherapy (LOF); clinical remission on dietary therapy plus immunosuppressive prednisone (LOP); and treatment failure (TXF). Eleven of 14 dogs were in clinical remission at the study end date (6 mo after enrollment): 6 LOF dogs and 5 LOP dogs. LOF dogs achieved a significant reduction in Canine Chronic Enteropathy Clinical Activity Index score and a significant increase in serum albumin within 2 wk of beginning dietary monotherapy. Four of 11 dogs in remission also had ultrasonographic evidence of resolution of linear striations. Low-fat diet appears to be an effective monotherapy in some dogs with presumptive PLE and ultrasonographic evidence of lymphangiectasia.