Objectives The extent to which menopause influences wellbeing is unclear. We investigated the association between moderate-severely bothersome vasomotor symptoms (VMS) and psychological general wellbeing in women, aged 40-65 years, taking into account socio-demographic and lifestyle factors. Study design/Main outcome measures This was a cross-sectional survey of 2020 Australian women, aged 40-65 years, recruited from the community between July 2013 and March 2014. Wellbeing was assessed by the Psychological and General Wellbeing questionnaire (PGWB) and VMS by the Menopause-specific Quality of Life Questionnaire. Results Moderate-severely bothersome VMS had a strong significant negative association with psychological general wellbeing [regression coefficient (?) = -8.17, 95 confidence interval (CI) -10.90 to -5.45]. Socio-demographic factors associated with lower wellbeing included being un-partnered (? = -2.80, 95 CI -4.74 to -0.86), obese (? = -5.46, 95 CI -7.24 to -3.68) and a smoker (? = -3.47, 95 CI -6.10 to -0.84). Older age (? = 0.29, 95 CI 0.06-0.42) and participation in paid and/or volunteer work (? = 2.72, 95 CI 0.61-4.82) were positively associated with wellbeing. For those with insecure housing, being a carer was associated with better wellbeing. Conclusions Moderate-severely bothersome VMS are significantly and independently negatively associated with psychological general wellbeing in women at midlife. This is an important consideration when assessing psychological wellbeing in women during this life phase.