Totally implantable vascular access devices (TIVADs) are commonly used in conjunction with enzyme replacement therapy (ERT) for lysosomal storage disorders (LSDs). This case series describes potential complications associated with long-term TIVAD use, such as compromise of skin integrity, infection, or port failures. Best practices and skilled specialists are essential for minimizing complications from long-term TIVAD use for ERT. Keywords: Mucopolysaccharidosis, Enzyme replacement therapy, Totally implantable venous access device, Lysosomal storage disorder