Background: Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE-in-PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI-in-PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN. Methods: This prospective randomized open-label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI-in-PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5–9. The percentages of blood glucose measurements at goal were compared between groups. Results: Sixty-seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day (P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI-in-PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI-in-PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI-in-PN (11.4%; P > .1). Conclusion: Both glargine insulin and RI-in-PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.