BACKGROUND: Medical image processing has gained much attention in developing computer-aided diagnosis (CAD) of diseases. CAD systems require deep understanding of X-rays, MRIs, CT scans and other medical images. The segmentation of the region of interest (ROI) from those images is one of the most crucial tasks. OBJECTIVE: Although active contour model (ACM) is a popular method to segment ROIs in medical images, the final segmentation results highly depend on the initial placement of the contour. In order to overcome this challenge, the objective of this study is to investigate feasibility of developing a fully automated initialization process that can be optimally used in ACM to more effectively segment ROIs. METHODS: In this study, a fully automated initialization algorithm namely, an adaptive Otsu-based initialization (AOI) method is proposed. Using this proposed method, an initial contour is produced and further refined by the ACM to produce accurate segmentation. For evaluation of the proposed algorithm, the ISIC-2017 Skin Lesion dataset is used due to its challenging complexities. RESULTS: Four different supervised performance evaluation metrics are employed to measure the accuracy and robustness of the proposed algorithm. Using this AOI algorithm, the ACM significantly (p≤0.05) outperforms Otsu thresholding method with 0.88 Dice Score Coefficients (DSC) and 0.79 Jaccard Index (JI) and computational complexity of 0(mn). CONCLUSIONS: After comparing proposed method with other state-of-the-art methods, our study demonstrates that the proposed methods is superior to other skin lesion segmentation methods, and it requires no training time, which also makes the new method more efficient than other deep learning and machine learning methods.