Abstract Background Low desire is the most common sexual problem in women at midlife. Prevalence data are limited by lack of validated instruments or exclusion of un-partnered or sexually inactive women. Aim To document the prevalence of and factors associated with low desire, sexually related personal distress, and hypoactive sexual desire dysfunction (HSDD) using validated instruments. Methods Cross-sectional, nationally representative, community-based sample of 2,020 Australian women 40 to 65 years old. Outcomes Low desire was defined as a score no higher than 5.0 on the desire domain of the Female Sexual Function Index (FSFI); sexually related personal distress was defined as a score of at least 11.0 on the Female Sexual Distress Scale–Revised; and HSDD was defined as a combination of these scores. The Menopause Specific Quality of Life Questionnaire was used to document menopausal vasomotor symptoms. The Beck Depression Inventory–II was used to identify moderate to severe depressive symptoms (score ≥ 20). Results The prevalence of low desire was 69.3% (95% CI = 67.3–71.3), that of sexually related personal distress was 40.5% (95% CI = 38.4–42.6), and that of HSDD was 32.2% (95% CI = 30.1–34.2). Of women who were not partnered or sexually active, 32.4% (95% CI = 24.4–40.2) reported sexually related personal distress. Factors associated with HSDD in an adjusted logistic regression model included being partnered (odds ratio [OR] = 3.30, 95% CI = 2.46–4.41), consuming alcohol (OR = 1.48, 95% CI = 1.16–1.89), vaginal dryness (OR = 2.08, 95% CI = 1.66–2.61), pain during or after intercourse (OR = 1.63, 95% CI = 1.27–2.09), moderate to severe depressive symptoms (OR = 2.69, 95% CI 1.99–3.64), and use of psychotropic medication (OR = 1.42, 95% CI = 1.10–1.83). Vasomotor symptoms were not associated with low desire, sexually related personal distress, or HSDD. Clinical Implications Given the high prevalence, clinicians should screen midlife women for HSDD. Strengths and Limitations Strengths include the large size and representative nature of the sample and the use of validated tools. Limitations include the requirement to complete a written questionnaire in English. Questions within the FSFI limit the applicability of FSFI total scores, but not desire domain scores, in recently sexually inactive women, women without a partner, and women who do not engage in penetrative intercourse. Conclusions Low desire, sexually related personal distress, and HSDD are common in women at midlife, including women who are un-partnered or sexually inactive. Some factors associated with HSDD, such as psychotropic medication use and vaginal dryness, are modifiable or can be treated with safe and effective therapies.