Background Mandibular first premolars have been reported to have complex anatomical aberration making them one of the most difficult teeth to manage endodontically. Objective To determine the root canal anatomy of mandibular first premolar in a Nepalese population using decalcification and clearing technique. Method One hundred and fifty extracted mandibular first premolars were collected from Nepalese population. Access cavities were prepared on the occlusal surface of each tooth. Teeth were decalcified by immerging in 5% nitric acid, dehydrated in ethyl alcohol and made transparent using methyl salicylate. Methylene blue dye was injected through access cavity and canal anatomy were observed and classified according to Vertucci's classification. Result The average length of mandibular first premolar was 20.43mm. One rooted teeth were 96% and two rooted were 4%. Vertucci's type I canal configuration was most prevalent (72%) followed by type V (18.6%), type III (3.3%), type II (2.6%) and type IV (2.6%). An unusual configuration was found in one tooth. Isthmus and apical deltas were found in 8.6%) and 14.6% of the cases respectively. Conclusion Type I canal configuration were the most frequently observed root canal configuration in mandibular first premolar followed by type V configuration. Such variation in root canal anatomy should be taken into consideration to ensure successful endodontic therapy of these teeth.