Abstract: Ball-sealer plugging is a cost-effective method for hydraulic fracturing in vertical wells, yet the transport and plugging behavior of ball sealers remains poorly understood. This paper investigates ball-sealer plugging using both experimental and numerical approaches. A coupled computational fluid dynamics (CFD) and discrete element method (DEM) model simulates ball transport under field conditions, validated by experiments in inclined pipes. Results show that plugging performance improves with a higher flow rate ratio of the perforation, allowing effective plugging even when the ball is far from the target perforation. There exists a threshold distance between the ball and the perforation under specific conditions. The closer the ball is to the wellbore wall, the higher the likelihood of successful plugging. Low-density balls can enhance plugging performance to some extent. At high flow rates, ball inertia along the wellbore axis increases, reducing the ball's ability to redirect and weakening plugging performance. Ball interactions also affect their positioning and plugging success. In vertical wells with multiple clusters, prioritizing higher flow rates to the first fracturing cluster optimizes overall plugging performance and minimizes excessive plugging in lower, under-stimulated clusters. These findings offer valuable insights for optimizing ball-sealer deployment in well completions, improving operational outcomes.