Background: Recognition of clinically significant bleeding (CSB) is vital for effective management of dengue patients. The primary objective was to identify the predictors of CSB among dengue patients and to formulate a simple scoring system. The secondary objective was to compare the grades of bleeding and severity of thrombocytopenia. Materials and methods: We conducted a retrospective study of adults aged above 18 years with dengue, admitted to the intensive care unit (ICU) of a tertiary care hospital in South India from 2015 to 2021. Demographic, clinical, and laboratory variables on admission were collected. The association of clinically significant bleeding with the above parameters was assessed by univariate and multivariate analysis. Results: A total of 9,817 dengue cases were hospitalized during the study period. A total of 120 patients with thrombocytopenia (<100000 cells/mm³) were admitted to the ICU and of them 38 (31.6%) had CSB. On univariate analysis fever, sequential organ function assessment (SOFA) score, elevated activated partial thromboplastin time (aPTT), and altered sensorium were significantly associated with CSB. The multivariate model identified SOFA score [adjusted odds ratio (aOR): 1.52; 95% confidence interval (CI): 1.11–2.08], temperature >38.3°C (aOR: 2.71; 95% CI: 1.1–6.47) and elevated aPTT > 40 seconds (aOR: 4.66; 95% CI: 1.42–15.3) as independent risk factors. A clinical predictive score was developed incorporating these three parameters. The performance of the score identified by the receiver operating characteristic (ROC) curve [area under the curve (AUC): 0.81; 95% CI: 0.73–0.91] demonstrated a sensitivity of 81% and specificity of 77%. Conclusion: This study revealed that temperature above 38.3°C, elevated aPTT, and an increase in SOFA score were identified as independent risk factors for CSB. A clinical predictive score derived from these variables can identify patients likely to develop CSB.