OBJECTIVES: To establish whether there are subsets of women with idiopathic menorrhagia who experience differential health-related quality of life (HRQL) benefits with LNG-IUS treatment, and which factors could be attributed to those differences. METHODS: Data for women with idiopathic menorrhagia residing in India, Russia and Turkey were derived from a prospective, 12-month observational study. Latent profile analysis (LPA) was used to identify unknown subgroups of differential responders on the Mental Component Summary (MCS) of the SF-36v2. Post hoc analyses were performed to characterize identified subgroups using baseline and 12 month data. RESULTS: Overall improvement in MCS scores from baseline to 12 months was 8.4 points. LPA analyses revealed two distinct subsets of patients: one smaller subset (30% of the sample) showed a smaller improvement (2.3 points) than the improvement overall and are thus referred to as ‘partial-responders.’ A larger subgroup (70% of the sample) was identified with a much greater improvement (11.3 points) than that overall, thus referred to as ‘responders’. Post hoc analyses revealed statistically significant differences between MCS responders and partial-responders:  significantly greater proportion of MCS responders had university-level education, were more likely to reside in India or Russia and be employed, reported‘none’ or ‘light’ bleeding intensity while on treatment,  reported greater patient and physician satisfaction with treatment, and had higher 12-month haemoglobin levels. CONCLUSIONS: Understanding of heterogeneity of treatment response is critical for routine clinical practice. Application of LPA identified two distinct subgroups of women showing differential response to HRQL from LNG-IUS treatment. All women showed a statistically significant improvement in HRQL as measured by the MCS, although this improvement was greater for a large subset of women in the sample. Country-level differences in treatment effect on mental HRQL may be subject to cultural or health care practice differences.