Background: Diabetes mellitus and hyperglycemia are associated with increased susceptibility to bacterial infections and poor treatment outcomes. This post hoc evaluation of the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) aimed to evaluate baseline characteristics, efficacy, and safety in patients with and without diabetes treated with ceftolozane/tazobactam and comparators. Ceftolozane/tazobactam is an antibacterial with potent activity against Gram-negative pathogens and is approved for the treatment of cIAI (with metronidazole) and cUTI (including pyelonephritis). Methods: Patients from the phase 3 ASPECT studies with (n = 245) and without (n = 1802) diabetes were compared to evaluate the baseline characteristics, efficacy, and safety of ceftolozane/tazobactam and active comparators. Results: Significantly more patients with than without diabetes were 65 years of age or older; patients with diabetes were also more likely to weigh >= 75 kg at baseline (57.1% vs 44.5%), to have renal impairment (48.5% vs 30.2%), or to have APACHE II scores >= 10 (33.8% vs 17.0%). More patients with diabetes had comorbidities and an increased incidence of complicating factors in both cIAI and cUTI. Clinical cIAI and composite cure cUTI rates across study treatments were lower in patients with than without diabetes (cIAI, 75.4% vs 86.1%, P = 0.0196; cUTI, 62.4% vs 74.7%, P = 0.1299) but were generally similar between the ceftolozane/tazobactam and active comparator treatment groups. However, significantly higher composite cure rates were reported with ceftolozane/tazobactam than with levofloxacin in patients without diabetes with cUTI (79.5% vs 69.9%; P = 0.0048). Significantly higher rates of adverse events observed in patients with diabetes were likely due to comorbidities because treatment-related adverse events were similar between groups. Conclusions: In this post hoc analysis, patients with diabetes in general were older, heavier, and had a greater number of complicating comorbidities. Patients with diabetes had lower cure rates and a significantly higher frequency of adverse events than patients without diabetes, likely because of the higher rates of medical complications in this subgroup. Ceftolozane/tazobactam was shown to be at least as effective as comparators in treating cUTI and cIAI in this population.