Background: Several studies indicate that quality of life (QoL) is impaired in middle aged women. Assessment of QoL using a single validated tool in Latin American climacteric women has not been reported to date at large scale. Objective: The Menopause Rating Scale (MRS) was used to assess QoL among middle aged Latin American women and determine factors associated with severe menopausal symptoms (QoL impairment). Methods: In this cross-sectional study, 8373 healthy women aged 40-59 years, accompanying patients to healthcare centres in 18 cities of 12 Latin American countries, were asked to fill out the MRS and a questionnaire containing socio-demographic, female and partner data. Results: Mean age of the entire sample was 49.1 ± 5.7 years (median 49), a 62.5% had 12 or less years of schooling, 48.8% were postmenopausal and 14.7% were on hormonal therapy (HT). Mean total MRS score (n = 8373) was 11.3 ± 8.5 (median 10); for the somatic subscale, 4.1 ± 3.4; the psychological subscale, 4.6 ± 3.8 and the urogenital subscale, 2.5 ± 2.7. The prevalence of women presenting moderate to severe total MRS scorings was high (>50%) in all countries, Chile and Uruguay being the ones with the highest percentages (80.8% and 67.4%, respectively). Logistic regression determined that impaired QoL (severe total MRS score ≥17) was associated with the use of alternatives therapies for menopause (OR: 1.47, 95% CI [1.22-1.76], p = 0.0001), the use of psychiatric drugs (OR: 1.57, 95% CI [1.29-1.90], p = 0.0001), attending a psychiatrist (OR: 1.66, 95% CI [1.41-1.96], p = 0.0001), being postmenopausal (OR: 1.48, 95% CI [1.29-1.69, p = 0.0001]), having 49 years or more (OR: 1.24, 95% CI [1.08-1.42], p = 0.001), living at high altitude (OR: 1.43, 95% CI [1.25-1.62, p = 0.0001]) and having a partner with erectile dysfunction (OR: 1.69, 95% CI [1.47-1.94, p = 0.0001]) or premature ejaculation (OR: 1.34, 95% CI [1.16-1.55, p = 0.0001]). Lower risk for impaired QoL was related to living in a country with a lower income (OR: 0.77, 95% CI [0.68-0.88], p = 0.0002), using HT (OR: 0.65, 95% CI [0.56-0.76], p = 0.0001) and engaging in healthy habits (OR: 0.59, 95% CI [0.50-0.69], p = 0.0001). Conclusion: To the best of our knowledge this is the first and largest study assessing QoL in a Latin American climacteric series with a high prevalence of impairment related to individual female and male characteristics and the demography of the studied population.