Ambulance service demand is increasing in the United Kingdom. A common speculative view makes a link between this rise in demand, deprivation, and certain medical conditions. This study explored factors influencing English ambulance service demand in two areas of differing socioeconomic status. Adopting a causal comparative design, the study compared the numbers of life-threatening calls that Yorkshire Ambulance Service receives and serves in two geographical areas within the Hull and East Riding area. The area of lower socioeconomic status generated significantly more life-threatening calls than the area of higher socioeconomic status; these calls often supported younger patients (mean age 59 years versus 71 years) for breathing difficulties (29% versus 14.5%) more commonly. Tackling inequality will require a whole-systems approach, effective leadership, and recognition of the benefits of understanding difference. A key relationship will entail engaging with seldom heard communities.