Background: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life.Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults.Design: Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining 1) the effects of "high versus low" protein intake or 2) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed.Results: Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, I²: 0%; n = 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures.Conclusions: Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751.