We investigated factors associated with treatment failure in the treatment of cutaneous leishmaniasis with meglumine antimony in a reference service in Mato Grosso State. A retrospective cohort of 151 patients with cutaneous leishmaniasis was built using medical records. The incidence of therapeutic failure was 47% (IC95%=39.2%-55%). Antimoniate doses below 10 mg/kg/day (RR=1.8; IC95: 1.1-3.0), previous leishmaniasis treatment (RR=1.7; IC95: 1.3-2.4), 3 or more skin lesions (RR=1.9; IC95: 1.4-2.5), incomplete treatment (RR=1.9; IC95: 1.3-2.6) and body weight above 68 kg (RR=1.7; IC95: 1.1-2.5) were associated with therapeutic failure. After adjustment, therapeutic failure was associated with having 3 or more cutaneous lesions (OR=4.6; IC95%=1.2-17.4), reports of previous leishmaniasis treatment (OR=4.5; IC95%=1.1-17.5), body weight above 68 kg (OR=4.3; IC95=1.5-11.9) and incomplete treatment schedule (OR=12.5; IC95%=2.1-75.4), although body weight is possibly associated with treatment failure due to the limitation of the maximum daily dose. These results help to identify patients at risk of treatment failure of cutaneous leishmaniasis with antimony therapy.