INTRODUCTION: Characterizing progression in Alzheimer's disease is critically important for early detection and targeted treatment. The objective was to develop a prognostic model, based on multivariate longitudinal markers, for predicting progression-free survival in patients with mild cognitive impairment. METHODS: The information contained in multiple longitudinal markers was extracted using multivariate functional principal components analysis and used as predictors in the Cox regression models. Cross-validation was used for selecting the best model based on Alzheimer's Disease Neuroimaging Initiative-1. External validation was conducted on Alzheimer's Disease Neuroimaging Initiative-2. RESULTS: Model comparison yielded a prognostic index computed as the weighted combination of historical information of five neurocognitive longitudinal markers that are routinely collected in observational studies. The comprehensive validity analysis provided solid evidence of the usefulness of the model for predicting Alzheimer's disease progression. DISCUSSION: The prognostic model was improved by incorporating multiple longitudinal markers. It is useful for monitoring disease and identifying patients for clinical trial recruitment.