Objective: Pain may not resolve, and even new painful conditions may arise in a certain proportion of patients after vertebroplasty/ kyphoplasty procedure performed for vertebral compression fractures. This study assessed the efficacy of targeting multiple pain generators, i.e., simultaneous use of vertebroplasty and epidural injections, in patients with vertebral compression fractures. Materials and Methods: A total of 58 patients who underwent percutaneous vertebroplasty (PVP) at the lumbar level because of osteoporotic compression fracture of the lumbar vertebra were included in this retrospective study. The patients received PVP alone or PVP plus epidural injection. The two groups were compared in terms of pain severity using visual analog scale (VAS) as well as Oswestry disability index (ODI) scores during the 3-month follow-up period. Additionally, requirements for narcotic analgesics and additional interventions were compared. Results: The two groups did not differ regarding the change in VAS scores over time (p=0.201). They differed regarding ODI scores, where the vertebroplasty plus epidural group had significantly lower ODI scores at 1 week (22.4±3.6 vs. 17.2±2.8), 1 month (21.1±3.8 vs. 15.7±2.4) and 3 months (22.9±5.5 vs. 15.0±2.7) (p<0.001 for all). Additionally, more patients in the vertebroplasty alone group required additional intervention (28.6% vs. 3.3%, p=0.011) and more were still requiring narcotics at three months (32.1% vs. 6.7%, p=0.013). Conclusion: Interlaminar epidural injections combined with PVP appear superior to PVP alone in improving lumbar function and in reducing the need for additional narcotics and interventions after such procedures. Further studies are warranted to confirm these observations.