Hand infection has been associated with increased morbidity in people with diabetes mellitus. PURPOSE: This study was conducted to determine risk factors for hand wound infection in patients with diabetes mellitus. METHODS: A 1:3 matched prospective case-control study was conducted from December 2006 to December 2016. All study patients were consecutively identified through the inpatient records upon admission to the University of the Philippines Manila, Philippine General Hospital (Manila, Philippines), for a hand wound infection necessitating surgical treatment and were followed until hospital discharge, wound healing, or death. Adults (≥18 years old) with diabetes mellitus for at least 6 months and with (study group) or without (control group) a hand wound infection were eligible to participate. Persons with a history of amputation or who were in a chronic debilitated state were excluded. Infection was defined as the presence of inflammation and purulent discharge. Eligible control patients were consecutively recruited from the outpatient clinics and were matched to the study patients by age (± 5 years) and gender. Demographic (eg, age, gender, education, occupation, tobacco use) and clinical data (body mass index [BMI], duration of diabetes, HbA1c levels, wound location and duration, delay in treatment, neuropathy, surgical procedures, length of hospital stay, and presence of arteriovenous [AV] fistula) were collected from patient records and entered into Excel spreadsheets for analysis. Regression analysis was performed and reported as odds ratio (OR) with 95% confidence intervals (CI). Level of significance was set P <.05. RESULTS: Participants included 30 study and 90 control patients. No significant differences between study and control patients were noted in terms of BMI, duration of diabetes, presence of peripheral neuropathy, occupation, or education. Significantly more study patients had elevated HbA1c (86 vs. 30; P = .0001), used tobacco (17 vs. 8; P = .0001), and had an AV fistula (3 vs. 0; P = .015). After multivariate analysis, HbA1c ≥48 mmoL/moL (OR = 18.8; 95% CI: 2.3-153.8; P = .006) and tobacco use (OR = 10.7; 95% CI: 3.5-32.7; P = .0001) were identified as independent risk factors for hand/upper extremity infection. CONCLUSION: Patients with diabetes who smoked or exhibited elevated HbA1c levels were at higher risk of having a hand infection. Further research and efforts to help people with diabetes stop smoking and maintain good glycemic control may help decrease the burden of hand infection.