Objective: To compare precorrectional and postcorrectional femoral alignment following distal femoral osteotomy using patient-specific 3-dimensional (3D)-printed osteotomy and reduction guides in vivo and ex vivo. Study design: Prospective study. Sample population: Ten client-owned dogs and matching 3D-printed plastic bone models. Methods: Distal femoral osteotomy was performed via a standard approach using osteotomy and reduction guides developed with computer-aided design software prior to 3D-printing. Femoral osteotomy and reduction was also performed on 3Dprinted models of each femur with identical reprinted guides. Femoral varus angle (FVA) and femoral torsion angle (FTA) were measured on postoperative computed tomographic images by 3 observers. Results: In vivo, the mean difference between target and achieved postoperative was 2.29 (±2.29 , P = .0076) for the FVA, and 1.67 (±2.08 , P = .300) for the FTA. Ex vivo, the mean difference between target and achieved postoperative was 0.29 (±1.50 , P = .813) for the FVA, and −2.33 (±3.21 , P = .336) for the FTA. Intraobserver intraclass correlation coefficients (ICC; 0.736-0.998) and interobserver ICC (0.829 to 0.996) were consistent with an excellent agreement. Conclusion: Use of 3D-printed osteotomy and reduction guides allowed accurate correction of FTA in vivo and both FVA and FTA ex vivo. Clinical significance: Use of 3D-printed osteotomy and reduction guides may improve the accuracy of correction of femoral alignment but warrant further evaluation of surgical time, perioperative complications, and patient outcomes compared with conventional techniques.