The aim of the study was to evaluate factors predicting severe symptomatic laboratory-confirmed (via Reverse transcription polymerase chain reaction, RT-PCR polymerase chain reaction) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection.This is a nationwide retrospective cohort study that was conducted in Mexico.Data from 258 reinfection cases (at least 28 days between both episodes onset) were analyzed. We used risk ratios (RRs) and 95% confidence intervals (CIs) to evaluate predictors of severe (dyspnea requiring hospital admission) secondary SARS-CoV-2 infection.The risk of severe disease was 14.7%, and the observed overall fatality rate was 4.3%. Patients with more serious primary disease were more likely to develop severe symptoms (39.5% vs. 5.5%, P