To evaluate whether the use of multiple displacement amplification (MDA) as the first step could increase the diagnosis efficiency of preimplantation genetic diagnosis (PGD) for α-thalassemia. Retrospective study. We retrospectively analyzed 632 PGD cycles of α-thalassemia that were included in our center between January 2014 to December 2017. In this study, we divided patients into two groups based on two different detection methods. Embryos were biopsied on day 3 post-insemination or at the blastocyst stage. For the polymerase chain reaction (PCR) group(n=313), fluorescent gap PCR were performed directly after cells lysis. For the MDA+ PCR group(n=319), whole genome of single cell(s) were directly amplified using MDA and its products were diluted 1: 100 and then detected by fluorescent gap PCR for α-thalassemia. a total of 5441 embryos were diagnosed, of which 3064 embryos were diagnosed in the PCR group and 2377 embryos were diagnosed in the MDA+PCR group. No statistical differences were found in the baseline characteristics between two groups. However, a higher overall diagnostic efficiency was observed in the MDA+PCR group(96.51% versus 86.16%, P <0.01). Moreover,the rate of embryos available for transfer was significantly higher in the MDA+PCR group than in the PCR group (71.62% versus 62.23%, P<0.01). In addition, there was a statistically significant difference in the carrier rates between the two groups (MDA+PCR group:46.38% versus PCR group:31.74%, P <0.01). Furthermore, misdiagnosis rate was lower in the MDA+PCR group than in the PCR group, but it was not statistically significant (0% versus 1.84%, P=0.317). Besides, the implantation rate was significantly higher in the MDA+PCR group than in the PCR group (50.36% versus 40.23%, P <0.01). Clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, and live birth rate were similar in both groups. When MDA is used as the first step, diagnosis efficiency may be increased. It is highly effective for PGD for α-thalassemia and deserve wide usage.