Treatments with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs) may delay the development of albuminuria in patients with early diabetic nephropathy. However, evidence in the literature has not been consistent. The present meta-analysis aimed to compare the short- and long-term therapeutic effects of ACE inhibitors and CCBs (when used separately) for preventing the progression of nephropathy in patients with diabetes mellitus. A comprehensive search of various databases was performed from inception until March 2015 for studies in the Chinese and English languages. Randomized controlled trials (RCTs) comparing the efficacy of ACE inhibitors with that of CCBs in patients with early diabetic nephropathy were considered. A total of 12 RCTs were included with a total of 947 patients. ACE inhibitors were indicated to be more effective in reducing the albumin excretion rate than CCBs after short-term treatments (<6 months) [mean difference (MD), 32.35; 95% confidence interval (CI), 31.62-33.07; P<0.00001]. There was no difference in serum creatinine values after treatment with either drug (MD, 8.7; 95% CI, -21.5-38.91; P=0.57). Data from six studies were used to compare long-term treatment effects (≥1 year). In terms of progression to normoalbuminuria, a marginal difference was obtained between the two drugs with better outcomes with ACE inhibitors [odds ratio (OR), 0.70; 95% CI, 0.49-1.00; P=0.05]. There was no statistically significant difference between ACE inhibitors and CCBs regarding the progression from microalbuminuria to macroalbuminuria (OR, 1.78; 95% CI, 0.82-3.87; P=0.15). In conclusion, the present study indicated that the antiproteinuric efficacy of CCBs may be less than that of ACE inhibitors after short-term treatment in patients with DN. However, both types of drugs are equally effective in reducing the progression of microalbuminuria to macroalbuminuria in the long term. Copyright: © Liang et al.