What would be the best persistence method for F5 to load balance traffic from clients...

When clients connect through a single source IP (NAT) — such as a corporate proxy or carrier-grade NAT — Source Address Affinity persistence becomes entirely ineffective because all clients share an identical source IP address. This would force every client session to the same pool member, completely eliminating even distribution and defeating the purpose of load balancing.

Cookie Persistence is the optimal solution in this scenario because it operates at Layer 7 , inserting a unique cookie into each client ' s HTTP/HTTPS response. Each individual browser session carries its own distinct cookie value, allowing the BIG-IP to identify and persist individual clients to specific pool members — regardless of whether they share a common source IP address. This guarantees both session persistence and even load distribution across pool members.

The remaining options are unsuitable because:

Destination Address Affinity persists based on destination IP, irrelevant for client-to-server session stickiness.

SSL Persistence uses the SSL Session ID for persistence, but SSL session IDs are frequently renegotiated and are unreliable for long-term persistence across modern TLS implementations.

Source Address Affinity fails entirely under NAT conditions as described.

Cookie persistence is the industry-standard method for HTTPS application load balancing requiring per-client session affinity.