The use of unrelated umbilical cord blood (UCB) as an alternative source of haematopoietic stem cells transplantation (HSCT) has been widely used for patients lacking a human leucocyte antigen (HLA) matched donor. One of the disadvantages of using UCB is the limited number of haematopoietic stem cells and, consequently, delayed engraftment and increased risk of early mortality. Many approaches have been investigated in the attempt to improve engraftment and survival. Among those, studies analysing prognostic factors related to patients, disease, donor and transplantation have been performed. Variable factors have been identified, such as factors related to donor choice (HLA, cell dose and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimens). This review will focus on the interactions between HLA, cell dose and other modifiable factors related to the UCB unit selection and transplantation that may improve outcomes after UCB transplantation.