OBJECTIVES: To identify treatment satisfaction thresholds for interpreting treatment–related changes in vasomotor symptoms, and determine the doses of desvenlafaxine succinate (DVS) that effectively provide relief of vasomotor symptoms considered important by menopausal women. METHODS: Efficacy and treatment satisfaction were assessed in 620 postmenopausal women with =7 moderate-to-severe vasomotor symptoms/day participating in a double-blind, placebo-controlled trial randomized to placebo or DVS 50, 100, 150, or 200 mg. Number and severity of hot flushes and number of nighttime awakenings were recorded in daily diaries for 12 weeks of treatment. Responses to the Menopausal Symptoms Treatment Satisfaction Questionnaire at week 12 were compared with efficacy results. The treatment satisfaction threshold was anchored by the difference in the average symptom change among women reporting “neutral” satisfaction compared with women reporting “satisfied,” without deference to treatment group. RESULTS: Greater percentages of participants in the DVS groups reported being “satisfied” or “extremely satisfied” with daytime and nighttime control of hot flushes compared with placebo (57-75% versus 52%; P = 0.009 and 63-80% versus 54%; P = 0.003). These efficacy results were greatest in the 100 mg DVS group. The treatment satisfaction threshold was 1.64 for daytime hot flushes, 0.20 for the hot flushes severity score, and 0.42 for nighttime awakenings. Statistically significant efficacy outcomes with DVS 100 mg compared with placebo exceeded all treatment satisfaction thresholds. CONCLUSION: Among menopausal women in this study, the treatment satisfaction thresholds in vasomotor symptoms reduction over placebo were 1.64 hot flushes per day and about one nighttime awakening every other night. Exceeding these vasomotor symptoms change thresholds indicated that the 100 mg dose of DVS had achieved important and meaningful improvements from the participants' perspective. DVS is an effective option for treatment of vasomotor symptoms associated with menopause.