Aquilaria crassna (agarwood) has been used in traditional Asian medicine to treat vomiting, rheumatism, asthma, cough and inflammation. Despite the wide range of ethno-pharmacological use of agarwood, its anti-angiogenic effect has not previously been evaluated through systematic studies. Therefore, the aim of this study was to prepare essential oils extracts from the stem bark of A. crassna native to Malaysia, and determine their anti-proliferative and anti-angiogenic activities. Stem bark samples were extracted with 80% ethanol and hydrodistillation methods. The resulting essential oils from both extraction approaches were subjected for cytotoxic activity using four cancer cell lines and one normal cell line. Hydrodistilled essential oils displayed significant cytotoxic effect against HCT 116 cells with the lowest IC50 value calculated (28.0 ± 1.5 μg/mL). Furthermore, we have investigated the effect of hydrodistilled essential oils (active extract) on angiogenesis in vitro and ex vivo, and found that essential oils directly inhibited tube formation after plating endothelial cells on matrigel. In addition, essential oils caused significant inhibition of microvessels outgrowth of rat aortic ring assay in a dose-dependent manner (P<0.05) with an IC50 (43.13 μg/ml). The GC-MS analysis of the most active extract showed the presence of several potent phytochemicals such as β-caryophyllene, 1-phenanthrenecarboxylic acid, α-caryophyllene, benzenedicarboxylic acid and azulene. It can be concluded that the anti-cancer and anti-angiogenic effects of the essential oils could be due to the synergistic effect of the biologically active phytoconstituents.