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Background: Endemic regions of cutaneous leishmaniasis (CL) and intestinal helminthiasis overlap. CL treatment with systemic pentavalent antimonial drugs (Sb 5+ ) fails in 10%-30% of patients. The study objective was to assess the etiological role of intestinal helminthiasis in CL treatment failure., Methods: An unmatched case-control study was done in 4 CL treatment sites in Peru in 2012-2015. Cases were CL patients with Sb 5+ treatment failure; controls were CL patients with Sb 5+ treatment success. Patients with a parasitologically confirmed CL diagnosis who had received supervised Sb 5+ treatment and could be classified as cases or controls were eligible. The main exposure variables were intestinal helminthiasis and strongyloidiasis, diagnosed through direct examination, rapid sedimentation, Baermann, Kato-Katz, or agar culture of stool samples. Additional exposure variables were other infections (HIV, human T-lymphotropic virus 1, tuberculosis, hepatitis B, intestinal protozoa) and noninfectious conditions (diabetes, renal insufficiency, and immunosuppressive medication). Age, gender, CL history, probable exposure place, and Leishmania species were treated as potential confounders in multiple logistic regression., Results: There were 94 case and 122 control subjects. Overall, infectious and noninfectious comorbidities were frequent both among cases (64%) and controls (71%). The adjusted odds ratio (OR) for the association between any intestinal helminth infection and CL treatment failure was 0.65 (95% confidence interval [CI], 0.30-1.38), and the adjusted OR for the association between strongyloidiasis and CL treatment failure was 0.34 (95% CI, 0.11-0.92)., Conclusions: In the Peruvian setting, high Sb 5+ treatment failure rates are not explained by intestinal helminthiasis. On the contrary, strongyloidiasis had a protective effect against treatment failure., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)