Objective Diabetic ketoacidosis and hyperosmolar hyperglycemic state are life-threatening hyperglycemic crises often requiring intensive care unit (ICU) management. Treatment includes intravenous (IV) insulin with a transition to subcutaneous (SC) insulin upon resolution. Hypoglycemia is a common complication associated with treatment of hyperglycemic crises, but risk factors have not been well established. This study aimed to assess risk factors associated with hypoglycemia during treatment for hyperglycemic crises. Methods This case-control study included ICU patients admitted with hyperglycemic crises at a single Veterans Affairs health system from 1 January 2013 to 31 March 2020. Patients who developed hypoglycemia during insulin treatment were compared with a control group. Odds of hypoglycemia were assessed based on risk factors, including BMI, comorbidities, and type of SC insulin used. Results Of 216 cases of hyperglycemic crises included, hypoglycemia occurred in 61 cases (44 on SC insulin, 11 on IV insulin, and 6 on both). Odds for hypoglycemia were significantly higher for underweight patients (odds ratio [OR] 4.52 [95% CI 1.05–19.55]), type 1 diabetes (OR 4.02 [95% CI 2.09–7.73]), chronic kidney disease (OR 1.94 [95% CI 1.05–3.57]), those resumed on the exact chronic SC insulin regimen following resolution (OR 2.91 [95% CI 1.06–7.95]), and patients who received NPH versus glargine insulin (OR 5.13 [95% CI 1.54–17.06]). No significant differences were seen in the other evaluated variables. Conclusion This study found several factors associated with hypoglycemia during hyperglycemic crises treatment, many of which are not addressed in consensus statement recommendations. These findings may help ICU clinicians prevent complications related to hyperglycemic crisis management and generate hypotheses for future studies.