Appendicitis is the most common surgical emergency encountered by the general surgeon. Literature has demonstrated that diabetics may manifest atypical signs of infection, often clouding the diagnostic picture. We conducted a 3-year retrospective analysis of adults with appendicitis to determine differences in presentation, diagnosis, treatment, and outcomes for diabetic versus nondiabetic patients. Demographics, symptoms, imaging, procedure(s), complications, and length of stay (LOS) were obtained via chart review. Factors were compared between patients with and without diabetes using chi-squared test, t test, or Mann-Whitney U test (significance at P ≤ 0.05). Multivariate regression analysis identified variables predicting longer LOS or perforation at diagnosis. Overall, 339 patients met inclusion criteria [303 were nondiabetic (ND), 36 were diabetic (D)]. On univariate analysis, diabetics were more likely to have other comorbid illnesses: obesity (P < 0.001), chronic kidney disease (P = 0.003), hypertension (P < 0.001), coronary artery disease (P < 0.001), peripheral vascular disease (PVD, P = 0.31), and chronic obstructive pulmonary disease (P = 0.002). Diabetics presented with lower white blood cell counts (mean 14.2 ND, 11.9 D, P = 0.02), and were more likely to present with perforation (18.5% ND, 38.9% D, P = 0.008). LOS was longer in diabetics (1.0 day for ND, 3.0 day for D, P < 0.001). Complications were more frequent in diabetics (19.4% D vs 8.6% ND), which trended toward but failed to reach significance (P = 0.066). On multivariate analysis, however, old age was the only characteristic associated with perforation [odds ratio: 1.05 (1.02-1.06), P < 0.001], whereas diabetes, chronic obstructive pulmonary disease, and older age predicted longer LOS (P ≤ 0.001). Diabetics present a more complicated clinical picture having significantly more comorbidities and a trend toward postoperative complications necessitating a higher index of suspicion to detection complications. Further study is needed to evaluate the optimal diagnostic and management approach in this challenging population.