Can I be 100% certain that a PCIe x4 card will fit in a PCIe x16 slot?

If it's a motherboard slot you're talking about it means it's a x16 physical slot but there are only x4 electrical connections, meaning that

According to PCIE Expresscard , a x1 card can be inserted into the x4, x8, and x16 connectors 15 This is referred to as up

pcie 30 x1 slot If you have the option of multiple slots where at least one supports PCIe, it's worth considering your secondary slot for an SSD upgrade When combined

pcie x16 expansion slot Comments13 · Explaining PCIe Slots · NVME ADAPTERS