The safety and success of future space missions will depend on the ability of crewmembers and Mission Control to collaborate effectively, even when communication between them is delayed. Communication protocols—i.e., structured communication templates—were designed with the goal to facilitate space-ground collaboration under time-delayed conditions. Their effectiveness was assessed in several space-analog simulation studies. Method: Astronauts and astronaut-like volunteers received communication training prior to their missions. Missions included 2 to 4 days on which communication with Mission Control was delayed. Surveys were administered throughout the mission asking participants to rate the effectiveness of the protocols and their interactions with Mission Control and in a final survey to provide feedback on individual elements of the communication protocols. Results and Discussion: Participants rated the protocols as fairly effective. Their ratings also suggest that the protocols mitigated the negative impacts of communication delay. Participants’ ratings of individual protocol elements were generally high but also point to specific training needs and technology requirements.