To evaluate the therapeutic effects of dobutamine and nesiritide in the treatment of heart failure (HF), a meta-analysis of published studies was conducted. Computerized bibliographic databases in Chinese and English languages were carefully searched to identify the relevant literature. A total of 6 cohort studies were enrolled in current meta-analysis for statistical analyses. The effect of dobutamine and nesiritide in patients with HF was estimated by odds ratios (ORs) and 95% confidence interval (CI). Our results revealed a significantly higher survival rate in nesiritide-treated patients, compared with those treated with dobutamine (OR = 1.97; 95% CI, 1.43-2.71; P < 0.001). In addition, a lower readmission rate was also associated with the nesiritide-treated group in comparison with the dobutamine-treated group (OR = 1.96; 95% CI, 1.39-2.78; P < 0.001). A stratified analysis revealed that the subgroup of patients with HF treated with nesiritide showed higher survival outcomes than those patients with HF treated with dobutamine when follow-up period was greater than 6 months (OR = 1.70; 95% CI, 1.21-2.38; P = 0.002) but not under 6 months (P > 0.05). This indicated that nesiritide treatment had longer term benefits as well. Interestingly, based on the reason for readmission, a subgroup analysis of the HF subgroup and the "all-cause" subgroup showed that higher readmission rates were associated with dobutamine treatment in both subgroups (HF: OR = 2.71; 95% CI, = 1.51-4.83; P = 0.001; all-cause: OR = 1.64; 95% CI, 1.06-2.53; P = 0.026; respectively). Our results suggest that nesiritide therapy is associated with a lower in-hospital mortality rates and decreased readmission rates compared with dobutamine treatment in patients with HF.