Weight loss therapy of older adults with obesity is limited by weight loss–induced decrease in bone mineral density (BMD), whichcould exacerbate ongoing age-related bone loss and increase the risk for fractures. Therefore, it is recommended that weight losstherapy of older adults with obesity should include an intervention such as regular exercise to reduce the concomitant bone loss.However, the most appropriate exercise types to combine with weight loss therapy in this older population is unknown. In a random-ized controlled trial, we performed a head-to-head comparison of aerobic or resistance exercise, or both, during matched ~10%weight loss in 160 older adults with obesity. We measured changes in BMD (total hip, femoral neck, trochanter, intertrochanter,one-third radius, lumbar spine) and bone markers. Changes between groups were analyzed using mixed-model repeated measuresanalyses of variance. After 6 months of intensive lifestyle interventions, BMD decreased less in the resistance group (−0.006 g/cm2[−0.7%]) and combination group (−0.012 g/cm2[−1.1%]) than in the aerobic group (−0.027 g/cm2[−2.6%]) (p = 0.001 forbetween-group comparisons). Serum C-telopeptide, procollagen type 1 N-propeptide, and osteocalcin concentrations increasedmore in the aerobic group (33%, 16%, and 16%, respectively) than in the resistance group (7%, 2%, and 0%, respectively) and com-bination group (11%, 2%, and 5%, respectively) (p = 0.004 to 0.048 for between-group comparisons). Multiple regression analysesrevealed that the decline in whole body mass and serum leptin were the independent predictors of the decline in hip BMD (multipleR = 0.45 [p < .001]). These findings indicate that compared with aerobic exercise, resistance and combined aerobic and resistanceexercise are associated with less weight loss–induced decrease in hip BMD and less weight loss–induced increase in bone turnover.Therefore, both resistance and combined aerobic and resistance exercise can be recommended to protect against bone loss duringweight loss therapy of older adults with obesity. (LITOE ClinicalTrials.gov number NCT01065636.)