<p>Leishmaniasis is a vector-borne disease caused by <i>Leishmania</i> protozoa, transmitted through infected female phlebotomine sandflies. Cutaneous leishmaniasis (CL), its most common form, causes considerable morbidity, particularly among Colombian military personnel in endemic areas. Although meglumine antimoniate (MA) remains the first-line treatment, increasing reports of therapeutic failure (TF) raise concerns about its efficacy and highlight the need to identify associated risk factors.&#xa0;The objective of this study was to identify risk factors linked to MA treatment outcomes in Colombian soldiers with CL and to characterise the <i>Leishmania</i> species involved and their geographic distribution.&#xa0;A total of&#xa0;128 soldiers diagnosed with CL (2018–2019) were followed for treatment response. Sociodemographic, clinical and lesion data were collected. <i>Leishmania</i> species were identified through HSP70 and MPI gene barcoding, and geographic origins were mapped. Selected isolates from TF patients underwent in vitro susceptibility testing to MA.&#xa0;The cure proportion was 67.9%, with TF in 32%. Factors significantly associated with TF included previous infections (<i>p</i> = 0.001), prior MA use (<i>p</i> = 0.000), lymphadenopathy (<i>p</i> = 0.008) and lesion type (<i>p</i> = 0.002). Multivariate analysis identified previous treatment (<i>p</i> = 0.000), lesion size and infections acquired in the Orinoquía (<i>p</i> = 0.013) and Pacific (<i>p</i> = 0.014) regions as risk factors. <i>L. (V.) braziliensis</i> predominated, especially in Orinoquía and Amazon regions; <i>L. (V.) panamensis</i> was widespread, and <i>L. (L.) mexicana</i> appeared only in the Andean region. In vitro resistance to MA was not observed in analysed isolates; thus, this factor does not appear related to TF.&#xa0;TF is linked to specific clinical and epidemiological variables, supporting their integration into patient monitoring during MA therapy. Clinical trial number: not applicable</p>