Background The present study investigated the prognostic value of medical comorbidities at admission for 30-day in-hospital mortality in patients with acute myocardial infarction (AMI). Methods A total of 5161 patients with AMI were admitted in Chinese PLA General Hospital between January 1,1993 and December 31,2007. Medical comorbidities including hypertension, diabetes mellitus, previous myocardial infarction, valvular heart disease, chronic obstructive pulmonary disease (COPD), renal insufficiency, previous stroke, atrial fibrillation and anemia, were identified at admission. The patients were divided into 4 groups based on the number of medical comorbidities at admission (0, 1, 2, and ≥ 3). Cox regression analysis was used to calculate relative risk (RR) and 95% confidence intervals (CI), with adjustment for age, sex, heart failure and percutaneous coronary intervention (PCI). Results The mean age of the studied population was 63.9 ± 13.6 years, and 80.1% of the patients were male. In 74.6% of the patients at least one comorbidity were identified. Hypertension (50.7%), diabetes mellitus (24.0%) and previous myocardial infarction (12%) were the leading common comorbidities at admission. The 30-day in-hospital mortality in patients with 0, 1, 2, and ≥ 3 comorbidities at admission (7.2%) was 4.9%, 7.2%, 11.1%, and 20.3%, respectively. The presence of 2 or more comorbidities was associated with higher 30-day in-hospital mortality compared with patients without comorbidity (RR: 1.41, 95% CI: 1.13-1.77, P = 0.003, and RR: 1.95, 95% CI: 1.59-2.39, P = 0.000, respectively).Conclusions Medical comorbidities were frequently found in patients with AMI. AMI patients with more comorbidities had a higher 30-day in-hospital mortality might be predictive of early poor outcome in patients with AMI.