BACKGROUND: Timely and accurate detection of Mycobacterium leprae (M. leprae) is crucial for efficient treatment and early intervention of leprosy, which requires a simple and rapid extraction-free assay. METHODS: An HiFi-LAMP assay was developed for detection of M. leprae. The performance of the assay was assessed by comparing with qPCR and nested PCR assays using clinical samples. The extraction-free HiFi-LAMP assay was assessed by saliva from individuals with leprosy. RESULTS: The M. leprae HiFi-LAMP assay has high specificity and sensitivity with a limit of detection (LOD) of 43 copies/25 μL reaction. Both sensitivity and specificity of the assay were 100% for 130 purified DNA from nasal and oral samples, and the sensitivity was slightly higher than 50-88.9% by the qPCR assay. A higher detection rate of M. leprae was observed in nasal swabs than oral swabs. The extraction-free assay directly using 6 μL saliva that has a LOD of 11,833 M. leprae RLEP copies/mL saliva can be completed within 30 mins, and showed 66.7% sensitivity for three saliva samples when compared with the assay using purified DNA. CONCLUSION: The standard and/or extraction-free HiFi-LAMP assays can be used for detecting and monitoring M. leprae in endemic areas in resource-limited settings.