INTRODUCTION: Sickle cell trait (SCT) is a heterozygotic state defined by having one normal hemoglobin gene and one sickle hemoglobin gene. Individuals with SCT are at increased risk for negative health outcomes during intense physical exertion, especially in hot climates and high-elevation locations, or when dehydrated. The U.S. Air Force mitigates this risk through universal screening after accession followed by education of SCT-positive airmen. Airmen who are SCT positive but remain asymptomatic are not restricted in occupation choice or deployment/duty locations based on their SCT status. Previous studies have analyzed the relationship between SCT and health and fitness outcomes. The objective of this study was to analyze the relationship between SCT and career and operational outcomes in a large cohort of airmen and secondarily to analyze the relationship between hemoglobin S (HgbS) percentage and these outcomes. METHODS: This is a retrospective cohort study of all recruits who entered U.S. Air Force (USAF) Basic Military Training (BMT) between January 2009 and December 2013. The SCT status was assessed through a sickle solubility test. Hemoglobin electrophoresis permitted subgroup analysis of SCT-positive individuals by HgbS percentage. The following career and operational outcomes were assessed: BMT graduation; retention at 4 and 6 years; promotion to the rank of staff sergeant by 4 and 6 years; overseas deployment and number of deployments within 6 years; and high-elevation assignment and cumulative months at a high-elevation assignment within 6 years. Multivariable logistic regression was used to assess all binary outcomes, controlling for age, sex, and race, to produce adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Multivariable Poisson regression was used to assess cumulative count outcomes and to produce adjusted incidence rate ratios (aIRRs) with 95% CIs. Attrition from BMT by SCT status was also assessed as a hazards function using the Kaplan-Meier approach with Cox proportional hazards. RESULTS: A total of 180,355 civilians entered USAF BMT during the 5-year surveillance period, of whom 169,837 graduated and had data available for analysis. Compared to their SCT-negative peers, SCT-positive airmen (n = 1,697) had 26% lower adjusted odds of promotion to staff sergeant within 4 years of BMT graduation (aOR = 0.74; 95% CI: 0.59-0.92) and served less time at a high-elevation assignment during their first 6 years (aIRR = 0.88; 95% CI: 0.85-0.91). The SCT status was not associated with statistically significant differences in BMT graduation, retention at 4 and 6 years, promotion to staff sergeant by 6 years, likelihood or number of overseas deployments, and likelihood of ever working at a high-elevation assignment. Retention at 4 and 6 years was inversely associated with HgbS percentage. CONCLUSIONS: SCT-positive and SCT-negative airmen had similar career and operational outcomes, with two exceptions: SCT-positive airmen were less likely to be promoted to staff sergeant within 4 years, and they spent less time at a high-elevation location during their first 6 years of service. The underlying explanation of these findings should be explored with an aim to support SCT-positive airmen and to reduce potentially unwarranted discrepancies. Efforts should continue to reduce the stigma associated with SCT.