Objective This project quantifies operationally relevant measures of flight performance and workload in a high-fidelity long-duration spaceflight analog, longitudinally across mission duration, using a portable simulation platform. Background Real-time performance measures allow for the objective assessment of task performance and the timely identification of performance degradations. Methods Measures of flight performance on a piloted lunar lander task were collected on 32 total crewmembers across 8 simulated space missions of 45 days each (623 total sessions). Results Mission duration demonstrated a significant effect on measures of flight performance across all campaigns. Flight measures showed a general pattern of peaking in accuracy during the middle-late quartiles of overall mission time, then degrading again towards baseline. On the workload measure, however, a general linear decrease in workload consistent with progressive task learning was observed in both campaigns. Conclusion This investigation demonstrated the disruptive effect of time in mission on some, but not all, aspects of task performance. While mission interval differentially impacted measures of flight accuracy, workload, by contrast, seemed to steadily decrease with in-mission time. Application While more work is needed, the observed discrepancy between progression of flight performance and workload assessment highlights the importance of sensitive and specific measurement tools for the tracking of distinct performance metrics.