High dietary acid load may be detrimental to bone mineral density (BMD), although sufficient calcium intake might neutralize this effect. In observational studies, the association between BMD and dietary acid load, estimated by net endogenous acid production (NEAP) and potential renal acid load (PRAL), has been inconsistent, and the potential modifying effect of calcium intake has not been assessed. We therefore examined the cross-sectional associations of estimated NEAP and PRAL with BMD in the Framingham Osteoporosis Study. We hypothesized that higher estimated NEAP and PRAL would be associated with lower BMD, but only among those with total calcium intake < 800 mg/d. BMD of the femoral neck and lumbar spine was measured, and estimated NEAP and PRAL were calculated via FFQ among 1069 Framingham Original (1988-1989, 1992-1993; 62% women, mean age 76 y) and 2919 Offspring (1996-2001; 56% women, mean age 60 y) cohort participants. Cohort- and sex-specific ANCOVA was used to calculate multivariable-adjusted mean BMD for estimated NEAP and PRAL quartiles. Assuming no uncontrolled confounding, estimated NEAP, but not PRAL, was inversely associated with femoral neck BMD (P-trend = 0.04) in Original cohort men, whereas neither was associated with lumbar spine BMD. Estimated NEAP and PRAL were not associated with BMD at any site among Original cohort women or Offspring cohort men and women. There were no significant interactions between either estimated NEAP or PRAL and total calcium intake. These results suggest that, with a possible exception of older men, dietary acid load does not have a measureable negative effect on bone health, regardless of total calcium intake.