This study systematically evaluates the impact of timestep selection on the accuracy and reliability of alchemical free energy (AFE) simulations, challenging the widespread adoption of a 4 fs timestep with HMR and SHAKE constraints. Our findings reveal that larger timesteps, particularly 4 fs, introduce significant energy conservation issues and possible statistically unreliable free energy results, underscoring the need for context-specific guidelines in timestep optimization. These results have profound implications for computational drug design, where even small errors in binding affinity predictions can negatively impact lead optimization efforts.