Background Mucosal Leishmaniasis (ML) is a serious clinical form of leishmaniasis characterised by destruction of the oral, nasal or both mucosae. About 5-10% of patients that undergone Cutaneous Leishmaniasis (CL) can develop this complication. Risk factors associated to the occurrence of ML are not entirely clear. The presence of a RNA virus in the cytoplasm of the infecting parasite, known as Leishmania RNA virus (LRV), exacerbates the host¿s immune response and may contribute to the appearance of CL complicated forms. Methods A retrospective case-control study was conducted in 103 patients. Cases were defined as patients with ML (n=33) and controls correspond to patients that suffered from CL without mucosal lesions (n=70). Demographic, epidemiological and clinical data were recorded from patients¿ medical records. Detection of LRV type 1(LRV1) was achieved by RT-qPCR and Leishmania species identification by hsp70 PCR-RFLP and miniexon PCR in cryopreserved biopsies. In order to find risk factors associated with ML occurrence a bivariate and logistic regression analysis were carried out. Results Frequency of LRV1 in cases and control group was 33.3% and 8.6%, respectively and predominant Leishmania species in both groups was L. (V.) braziliensis. Multivariate logistic regression suggests that the factor associated with the occurrence of ML was the infection with Leishmania spp. carrying LRV1 [OR,6.81, 95%CI 1.46 ¿ 31.85 and p=0.015] while the infecting Leishmania species and other evaluated variables were not associated with ML occurrence. Conclusions The presence of LRV1 is associated with occurrence of ML in patients infected in Colombia with a significant OR of 6.81