Acute infection with Plasmodium vivax, classically associated with benign disease, has been presenting as serious and even fatal disease in recent years. Severe disease is mainly due to biochemical and hematological alterations during the acute phase of infection. In the present cross-sectional study, the aspartate aminotransferase-to-platelet ratio index (APRI) was evaluated as a method for identifying patients at risk of severe vivax malaria. This retrospective study included 130 patients with confirmed P. vivax infection between June 2006 and January 2018. Clinical-epidemiological data were obtained from medical records. Hematological and biochemical parameters were determined using automated equipment. The criteria of severity for infection by Plasmodium falciparum, established by the World Health Organization (WHO), were adapted to classify patients with danger signs of severe vivax malaria. Of the 130 patient's records evaluated, 19 (14.6%) had one or more signs and symptoms of severe malaria. The mean APRI values among patients with and without severe malaria were 2.11 and 1.09, respectively (p = 0.044). Among those with severe disease, the proportion with an APRI value above 1.50 was 30% compared to the 10% among those without severe disease (p = 0.007). The area under the receiver operating characteristic curve (95% CI), calculated to assess the accuracy of the APRI in discriminating between patients with and without severe disease, was 0.645 (0.494; 0.795). An APRI cutoff of 0.74 resulted in sensitivity of 74.0%, specificity of 56.0%, and accuracy of 65.0%. This study shows that the APRI is elevated in patients with evidence of infection by P. vivax. Based on the good sensitivity found in this study, we conclude that this simple index can serve as a diagnostic biomarker to identify patients at risk of severe disease during the acute phase of P. vivax infection.