Previous meta-analyses investigating blood pressure effects of anti-obesity drugs have included studies using non-licensed doses, but not data from head-to-head studies. Furthermore, although diabetes is an important comorbidity in obesity, variation in blood pressure effects across diabetes status has not been investigated. The objective of this study was to estimate the effects on systolic (SBP) and diastolic blood pressure (DBP) of orlistat and sibutramine. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles from 1990 to February 2009 were searched. All placebo-controlled randomized controlled trials of 12-month duration or randomized head-to-head studies of any duration on adults using standard doses were included. Studies/study arms were excluded if they only evaluated weight maintenance after weight loss. Randomized controlled trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Random effects models were used for assessment of weighted mean differences. Eighteen placebo-controlled (12 orlistat, 5540 patients; 6 sibutramine, 1495 patients) and four head-to-head trials (348 patients) met the inclusion criteria. Three orlistat and three sibutramine studies examined overweight subjects with type 2 diabetes (T2DM), as did two head-to-head trials. Mean baseline SBP ranged from 119 to 153 mmHg, and mean DBP from 69 to 98 mmHg. Overall, the placebo-controlled SBP change was -1.9 (95% CI; -2.7, -1.1) mmHg for orlistat, and 0.5 (-1.1, 2.1) mmHg for sibutramine. The corresponding values for DBP were -1.5 (-2.2, -0.8) and 1.7 (0.7, 2.6). Compared with patients without diabetes, diabetic patients treated with orlistat experienced smaller and non-significant reductions of SBP (-0.9; -2.6, 0.7 vs. -2.2; -3.0, -1.3) and DBP (-1.0; -2.4, 0.3 vs. -1.6; -2.4, -0.8). For sibutramine, higher on-treatment elevations in SBP (1.6; -1.3, 4.5 vs. 0.1; -1.8, 2.0) and DBP (2.4; 0.6, 4.1 vs. 1.4; 0.3, 2.5) were seen in patients with vs. without diabetes. In head-to-head trials, the overall differences between sibutramine and orlistat were small and non-significant for both SBP (1.0; -2.3, 4.3) and DBP (-0.2; -2.9, 2.5). In conclusion, in the studies using approved sibutramine doses, the drug caused significant elevations in DBP, while the overall SBP effect was near null. Moreover, absence of a blood pressure-lowering effect of orlistat ad a higher DBP elevation by sibutramine were observed for persons with diabetes. Head-to-head studies indicated that an indirect comparison of placebo-adjusted blood pressure effects may overestimate the adverse effects associated with sibutramine, but these studies were small, of shorter duration and of lower quality.