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PURPOSE To develop an online Graphic-Processing-Unit (GPU)-accelerated Monte-Carlo-based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address inter-fraction anatomical changes in patients treated with PBS. METHODS AND MATERIALS A four-step workflow was developed using our in-house developed GPU-accelerated Monte-Carlo-based treatment planning system to implement online Monte-Carlo-based ART for PBS. The first step conducts diffeomorphic demon-based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a re-optimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the re-opotimized plan in the third step. The fourth step involves a two-stage (before and after delivery) patient specific quality assurance (PSQA) of the re-optimized plan. The before-delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open-source Monte Carlo code, MCsquare. The after-delivery PSQA is to compare the plan dose to the dose re-calculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), Dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from re-optimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS. RESULTS For all three patients, the propagated contours were found to have good volume conformance [JI (lowest-highest: 0.833-0.983) and DSC (0.909-0.992)] but sub-optimal boundary coincidence [HD (2.37-20.76 mm)] for organs at risk (OARs). The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the inter-fractional anatomical changes. Re-optimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 seconds, excluding the time for manual intervention. CONCLUSION The proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a re-optimized plan that significantly improved the plan quality. This article is protected by copyright. All rights reserved.