Strategic infarction describes how lesions in particular locations have disproportionate effects on brain function. Strategic locations can reflect “bottlenecks” in functional networks for movement or cognition. Another hypothesis is that strategic effects are an emergent property of the brain’s network architecture. We aimed to examine the effect of simulated lesions on the global properties of the structural connectome. Simulated lesions were made in two sets of locations: i) subcortical nuclei recognised as sites of strategic infarction; ii) highly connected hubs that are part of the brain’s “rich club”, a group of highly interconnected hubs that mediate long-distance connectivity in the brain. 39 healthy volunteers aged 53-93 years underwent diffusion-weighted MRI. Whole-brain tractograms were represented as network graphs. Lesions were simulated by removing a node and its connections from the graph. The proportional change in network global efficiency due to each lesion was calculated. Lesions of rich-club nodes led to larger reductions in global efficiency than lesions outside the rich club. Lesions of the precunei produced the largest effect. Among subcortical nodes, vulnerability was highest for thalamic lesions. Age was positively correlated with vulnerability to lesions in the thalami. The structural connectome of healthy individuals aged over 50 is vulnerable to strategic lesions of rich-club nodes, though some of the key hubs are in sites rarely affected by stroke. The vulnerability of the structural connectome to thalamic stroke increases with age. This is likely to be a factor in the influence of age on stroke outcome.