Concerns have been raised about the adverse effect of fructose on blood pressure. International dietary guidelines, however, have not addressed fructose intake directly. A systematic review and meta-analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrates on systolic, diastolic, and mean arterial blood pressures. Studies were identified using Medline, Embase, and Cochrane databases (through January 9, 2012). Human clinical trials of isocaloric oral fructose exchange for other carbohydrate sources for ≥7 days were included in the analysis. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences with 95% CI. Heterogeneity was assessed by the Q-statistic and quantified by I ² . Study quality was assessed using the Heyland Methodological Quality Score. Thirteen isocaloric (n=352) and 2 hypercaloric (n=24) trials met the eligibility criteria. Overall, fructose intake in isocaloric exchange for other carbohydrates significantly decreased diastolic (mean difference: −1.54 [95% CI: −2.77 to −0.32]) and mean arterial pressure (mean difference: −1.16 [95% CI: −2.15 to −0.18]). There was no significant effect of fructose on systolic blood pressure (mean difference: −1.10 [95% CI: −2.46 to 0.44]). The hypercaloric fructose feeding trials found no significant overall mean arterial blood pressure effect of fructose in comparison with other carbohydrates. To confirm these results, longer and larger trials are needed. Contrary to previous concerns, we found that isocaloric substitution of fructose for other carbohydrates did not adversely affect blood pressure in humans.