Patients with osteoporosis and chronic kidney disease (CKD) are at increased risk of fracture and associated negative outcomes, including increased mortality. The present post hoc analysis of two randomized, multicenter, phase 3 clinical trials—Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) and Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH)—investigated the efficacy and safety of romosozumab in postmenopausal women with osteoporosis and mild-to-moderate CKD. The analysis included data from 7147 patients from FRAME and 4077 from ARCH. Eighty-one percent of patients from FRAME and 85% from ARCH had mild or moderate reduction in estimated glomerular filtration rate (eGFR) at baseline, and part of this reduction is likely age related. During the 1-year double-blind phases of the trials, patients received romosozumab 210 mg sc or placebo monthly in FRAME and romosozumab 210 mg sc monthly or alendronate 70 mg po weekly in ARCH. Bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck and vertebral and nonvertebral fractures were assessed at baseline and month 12. In both trials, the least-square mean percent change from baseline BMD was significantly greater in the romosozumab groups versus controls across all kidney function categories at month 12. Romosozumab reduced the relative risk of new vertebral fractures at month 12 among patients with eGFR of 30–59, 60–89, and ≥90 mL/min by 72% (95% confidence interval [CI] 14–91;​ p = 0.017), 70% (40–85;​ p < 0.001), and 84% (30–96;​ p = 0.005), respectively, in FRAME versus placebo, and by 51% (5–75;​ p = 0.04), 19% (−28 to 49;​ p = 0.39), and 57% (1–81, p = 0.04), respectively, in ARCH versus alendronate. Incidences of adverse events, asymptomatic decreases in serum calcium, and evolution of kidney function during the studies were similar across all baseline kidney function groups. Romosozumab is an effective treatment option for postmenopausal women with osteoporosis and mild-to-moderate reduction in kidney function, with a similar safety profile across different levels of kidney function.