Osteoporotic vertebral compression fracture (OVCF) is a serious complication of osteoporosis, and percutaneous vertebroplasty (PVP) is a major therapeutic method for OVCF. This study aimed to evaluate the clinical efficacy and postoperative complications of robot-assisted targeted PVP for the treatment of OVCF. The data from 202 OVCF patients were analyzed in this study, including 72 cases received traditional PVP (PVP group), 68 cases received robot-assisted PVP (R-PVP group), and 62 cases underwent robot-assisted PVP combined with targeted plugging (R-PVP + TP group). The fluoroscopic exposure conditions, operative duration, lengths of stay, postoperative bone cement leakage, refracture, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score were obtained and compared between the three groups. The Kaplan-Meier method and logistic regression model were adopted to screen the risk factors related with postoperative refracture. R-PVP and R-PVP + TP group had significantly reduced fluoroscopic frequency and radiation dose, and reduced cement leakage compared with PVP group. R-PVP + TP not only showed more obvious advantages in these aspects, but also had a lower probability of postoperative refracture. In addition, BMD, fracture vertebral distribution, cement leakage, and surgery methods were independent related with refracture. All the results demonstrated robot assistance could improve the application of PVP in the treatment of OVCF, and robot-assisted PVP combined with targeted plugging showed significantly reduced fluoroscopic exposure, bone cement leakage, and rate of postoperative refracture. BMD, fracture vertebral distribution, cement leakage, and operation methods were identified as four risk factors for the onset of refracture after PVP.