This study examines the generalizability of the latent structure of the Polish version of the Ego-Resiliency Scale (ER89-R12), a brief self-report scale that measures ego-resiliency. We investigated the measurement invariance, validity, and reliability of ER89-R12 among three groups of individuals who were facing various major, long-term, life-changing crises (N = 512): parents of children with Down’s syndrome, women with breast cancer, and individuals after divorce. The analysis of the measurement invariance confirmed the two-factor structure of the questionnaire and the high reliability of this measure in those studied groups. A multigroup confirmatory factor analysis provided evidence of configural, metric, scalar, and residual invariance across the three groups. Moreover, the correlation patterns were similar across the groups. Ego-resiliency was strongly and consistently positively correlated with mental health: psychological well-being, perceived social support, self-esteem, and post-traumatic growth, and negatively correlated with perceived stress. The presented results indicate the potential usefulness of the ER89-R12 tool in studies on people experiencing various crises in their lives.