Osteoporosis is a common complication of chronic liver disease, from cholestatic disorders to autoimmune, alcoholic, and posthepatitic cirrhosis. Osteoporosis appears more striking in patients with primary biliary cirrhosis (PBC) because the disease usually affects elderly women, who are naturally prone to osteoporosis. Our aims were (1) to compare the prevalence of osteoporosis (T-score ≤2.5 SD) between PBC patients and a group of age-and sex-matched controls consisting of healthy subjects from the general population; and (2) to identify the main risk factors for the development of bone loss. Thirty-three women with PBC (mean age, 47.3 ± 10.4 years) and 66 healthy subjects were enrolled in the study. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin, 25-hydroxyvitamin D (25-OH vit D), parathyroid hormone, and osteocalcin. Vertebral fractures were analyzed using vertebral fracture assessment (VFA). The mean T-score was lower in the PBC group compared to healthy controls, with a significant statistical difference (−2.39 ± 0.93 and −1.47 ± 0.99 in lumbar spine and total hip, respectively, in the PBC group versus −0.99 ± 0.51 and −0.56 ± 1.14 in healthy controls (P < 0.001). The prevalence of osteoporosis was 51.5% in the PBC group versus 22.7% in healthy controls with a statistically significant difference (P = 0.004). BMD of the PBC group was significantly correlated positively with body mass index (BMI) and 25-OH vit D, and negatively with menopausal status, duration of disease, and parathyroid hormone (PTH) levels. Vertebral fractures were present in 9% of the patients. We found that osteoporosis is more prevalent in women with PBC than in the general population. BMI, menopausal status, duration of the disease, and vitamin D deficiency are the main risk factors for osteoporosis in this liver disease.