OBJECTIVES We compared patient preference and satisfaction between two osteoporosis medications: alendronate (ALN 70mg tablets) taken orally once weekly (QW) and denosumab (DMAb 60mg; investigational agent) injected subcutaneously (SC) every 6 months (Q6M). METHODS Preference and satisfaction were evaluated as part of a phase 3, double-blind, double-dummy study to determine the effects of transitioning subjects from ALN to DMAb. Postmenopausal women ≥55 with a lumbar spine or total hip T-score ≤-2.0 and ≥-4.0 who were receiving ALN therapy for ≥6 months were eligible. After a 1-month ALN run-in phase, subjects were randomized to treatment with continued ALN QW + placebo injection SC Q6M or DMAb SC Q6M + QW placebo tablet. At study conclusion, subjects completed a 34-item questionnaire. Pre-determined endpoints of preference and satisfaction were measured by asking subjects to choose the tablet, the injection, or neither, in response to questions on preference ("Which do you prefer?") and satisfaction ("With which frequency of administration have you been more satisfied?"). RESULTS The subjects (n=251 ALN, n=253 DMAb) had a mean age of 67.6 years and a median length of prior bisphosphonate use of 36 months (range 6 to 192). 483 (95.8%) women took the questionnaire (240-ALN, 243-DMAb). Of the subjects who responded to the question on preference (240-ALN, 240-DMAb) or satisfaction (237-ALN, 242-DMAb), significantly more subjects preferred a 6-month injection vs a weekly oral tablet (ALN:66%-Q6M injection, 19%-QW tablet, 15%-neither, p<0.0001; DMAb:70%-Q6M injection, 19%-QW tablet, 12%-neither, p<0.0001) and significantly more subjects reported greater satisfaction with the frequency of 6-month vs weekly dosing (ALN:68%-Q6M injection, 19%-QW tablet, 14%-neither, p<0.0001; DMAb:70%-Q6M injection, 16%-QW tablet, 14%-neither, p<0.0001). CONCLUSIONS A preference for and a greater satisfaction with a 6-month injection vs a weekly oral tablet was demonstrated in subjects previously receiving and tolerating ALN therapy.