Objective. This current research is aimed at assessing clinical efficacy and prognosis of three-dimensional (3D) printing assisted patient-specific instrument (PSI) osteotomy guide in precise osteotomy of adult talipes equinovarus (ATE). Methods. We included a total of 27 patients of ATE malformation (including 12 males and 15 females) from June 2014 to June 2018 in the current research. The patients were divided into the routine group (
n
=
12
) and 3D printing group (
n
=
15
) based on different operative methods. The parameters, including the operative time, intraoperative blood loss, complications, time to obtain bony fusion, functional outcomes based on American Orthopedic Foot and Ankle Society (AOFAS), and International Congenital Clubfoot Study group (ICFSG) scoring systems between the two groups were observed and recorded regularly. Results. The 3D printing group exhibits superiorities in shorter operative time, less intraoperative blood loss, higher rate of excellent, and good outcomes presented by ICFSG score at last follow-up (
P
<
0.001
,
P
<
0.001
,
P
=
0.019
) than the routine group. However, there was no significant difference exhibited in the AOFAS score at the last follow-up and total rate of complications between the two groups (
P
=
0.136
,
P
=
0.291
). Conclusion. Operation assisted by 3D printing PSI osteotomy guide for correcting the ATE malformation is novel and feasible, which might be an effective method to polish up the precise osteotomy of ATE malformation and enhance the clinical efficacy.