The disclosed tamper-evident closure (100) encloses a medical access device, such as a vascular access device (200), such that it will be visibly apparent if the medical access device contained in the tamper-evident closure becomes exposed. The tamper-evident closure cannot be reapplied over the medical access device in a way to look the same as it did prior to exposing the medical access device. The tamper-evident closures comprise a holding cavity (110), a securing mechanism (160), and an apparent release. The disclosed tamper-evident closures are well suited for securing a medical access device that has an access point for delivering fluid to a patient or removing fluid from a patient.