The changes that occur in sex hormone levels, body composition, and lipid/lipoprotein levels during the menopause transition, together with vascular remodeling, increase the risk of cardiovascular disease (CVD) in postmenopausal women. Any treatments prescribed for concomitant conditions during menopause should not exacerbate CVD risk factors. Ospemifene is the first non-hormonal, non-estrogenic drug approved to treat moderate-to-severe vulvovaginal atrophy (VVA), a component of genitourinary syndrome of menopause, in women unsuited to receive vaginal estrogen therapy. This case study reports the experience of a postmenopausal woman with VVA who required escalation from local therapy and presented CVD risk factors (family history and hypertension). During the first 6 months of ospemifene treatment, and before initiating concomitant simvastatin for persistently elevated total cholesterol concentrations, improvements were observed in several lipid parameters (decreases of 11% in total cholesterol, 16% in low density lipoprotein cholesterol, and 15% in triglycerides) which may have been attributable at least in part to ospemifene. Improvements in lipid parameters during ospemifene treatment for VVA may contribute toward reducing long-term CVD risk.