A tripod cylindrical film hole with asymmetric side holes is studied numerically and experimentally on a flat plate for higher film cooling effectiveness. First, the influences of geometrical parameters are studied and the optimum configurations of the asymmetric tripod hole are found in a design of experiments (DoE) optimization study based on an improved numerical model for film cooling prediction, in which more than 100 3D computational fluid dynamics (CFD) simulations are carried out. Then, one optimum configuration of the asymmetric tripod hole is examined experimentally using pressure-sensitive paint (PSP) measurements and compared to the experimental results of the simple cylindrical film hole and a well-designed shaped film hole. The flow and heat transferring characteristics of the asymmetric tripod holes were explored from the DoE results. The side holes can form a shear vortex system or an antikidney vortex system when proper spanwise distances between them are adopted, which laterally transports the coolant and form a favorable coolant coverage. According to the experimental results on flat plate, the optimal configuration of the asymmetric tripod hole is significantly better than cylindrical hole, especially at high blowing ratios. Furthermore, it can provide equivalent or even higher film cooling effectiveness than a well-designed shaped hole.