Percutaneous vertebroplasty (PVP) is widely used to treat painful osteoporotic vertebral compression fractures (OVCFs), yet the comparative value of unilateral vs. bilateral access remains debated. The aim of this study was to compare unilateral and bilateral percutaneous vertebroplasty performed under local anaesthesia in patients with single-level OVCFs. This randomised study was conducted on 196 adults (mean age 71.7 ± 6.5 years) with single-level OVCFs treated under local anaesthesia and followed at baseline, discharge, and at the 6-month follow-up. Patients were allocated to unilateral or bilateral PVP. The primary outcomes were pain assessed on the visual analogue scale (VAS) and disability evaluated with the Oswestry Disability Index (ODI). Secondary endpoints included operative and fluoroscopy time, cement volume, vertebral body height restoration, kyphotic angle correction, and complications. Both techniques achieved rapid and significant pain relief, evident at discharge and sustained through the 6-month follow-up. Similarly, ODI demonstrated parallel improvement in both groups. Mean operative and fluoroscopy time was significantly shorter for unilateral PVP (27.4 ± 2.4 min) than with bilateral PVP (42.4 ± 3.0 min, p < 0.001), and fluoroscopy time was reduced by nearly 40% (58.2 ± 9.0 s vs. 93.8 ± 8.5 s, p < 0.001). No significant differences were found in vertebral height restoration and kyphotic angle correction. Cement volume was significantly lower with unilateral PVP (3.9 ± 0.4 mL) compared to bilateral PVP (5.8 ± 0.5 mL, p < 0.001). Complication rates were low and comparable, with cement leakage observed in 7.1% of unilateral and 8.2% of bilateral cases, and new adjacent fractures in 5.1% vs. 8.2% respectively. Unilateral PVP confers some procedural advantages (time, radiation, cement use) without compromising clinical or radiographic outcomes at 6 months.