BACKGROUND: Sustainable employability is increasingly important with current socio-economic challenges. Screening for resilience could contribute to early detection of either a risk, or a protector for sustainable employability, the latter being operationalized as workability and vitality. OBJECTIVE: To study the predictive value of Heart Rate Variability (HRV) measurements and the Brief Resilience Scale (BRS) for worker self-reported workability and vitality after 2-4 years. METHODS: Prospective observational cohort study with mean follow-up period of 38 months. 1,624 workers (18-65 years old) in moderate and large companies participated. Resilience was measured by HRV (one-minute paced deep breathing protocol) and the BRS at baseline. Workability Index (WAI), and the Vitality dimension of the Utrecht Work Engagement Scale-9 (UWES-9-vitality) were the outcome measures. Backward stepwise multiple regression analysis (p < 0.05) was performed to evaluate the predictive value of resilience for workability and vitality, adjusted for body mass index, age and gender. RESULTS: N = 428 workers met inclusion criteria after follow-up. The contribution of resilience, measured with the BRS, was modest but statistically significant for the prediction of vitality (R2 = 7.3%) and workability (R2 = 9.2%). HRV did not contribute to prediction of workability or vitality. Age was the only significant covariate in the WAI model. CONCLUSION: Self-reported resilience modestly predicted workability and vitality after 2-4 years. Self-reported resilience may provide early insight into the ability of workers to stay at work, although caution must be applied because explained variance was modest. HRV was not predictive.