Rationale: Airway remodeling in asthma involves accumulation of airway smooth muscle (ASM) and increased vascularity due to angiogenesis. Bronchial blood vessels and ASM are found in close proximity, and ASM releases multiple proinflammatory mediators including vascular endothelial growth factor (VEGF). Objective: We examined if release of proangiogenic mediators is increased in ASM from subjects with asthma and if this is translated to induction of angiogenesis. Methods: Biopsy-derived ASM cells were cultured from 12 subjects with mild asthma, 8 with moderate asthma, and 9 healthy controls. Angiogenesis induced by cell-conditioned medium (CM) from ASM was evaluated in a tubule formation assay. Anti-CD31 labeled tubules were quantified by image analysis. Angiogenic factors in CM were quantified by antibody arrays and by ELISA. Measurements and Main Results: Induction of angiogenesis by CM from unstimulated ASM was increased in subjects with mild asthma (2-fold) and moderate asthma (3-fold), compared with healthy CM (p<0.001). Levels of angiogenic factors (VEGF, angiopoietin [Ang]-1, angiogenin) were similarly elevated in CM from asthmatics compared with healthy subjects (p<0.05), whereas antiangiogenic factors (endostatin, Ang-2) were unchanged. VEGF, Ang-1, and angiogenin in combination increased vascularity (2-fold, p<0.01) in cultured intact biopsies. Selective VEGF immunodepletion abolished enhanced tubule formation by CM from asthmatic ASM (p<0.01), but CM depletion of Ang-1 or angiogenin had no effect. Conclusions: ASM cultured from subjects with mild or moderate asthma, but not healthy controls, promotes angiogenesis in vitro. This proangiogenic capacity resides in elevated VEGF release and suggests that ASM regulates airway neovascularisation in asthma.