Abstract Study question Is the quality of life (QoL) and psychological health affected by the duration of infertility in infertile women? Summary answer The duration of infertility negatively impacts infertile women's QoL and psychological health. What is known already Infertility is a deeply distressing experience. The process, from suspicion to received diagnosis and treatments often endures over a long period of time and usually involves repeated oscillations between hope and delusion, perception of loss of control, loss of self-esteem, inability to plan future, changes in identity and worldviews and difficulties in social interactions. Therefore, being infertile and undergoing fertility treatments is a condition which affects all infertile couple’s QoL. Whether QoL of these individuals is affected by the duration of infertility should be the focus of further investigation, to define psychological care interventions with patients dealing with infertility. Study design, size, duration This transversal study enrolled 442 female infertile patients that completed a modified non-validated Fertility Quality of Life Questionnaire (FertiQoL) between August and November 2021, containing multiple choice questions, which were evaluated in an ordinal manner (from one to five, being five the reference category associated with best QoL parameter). Participants/materials, setting, methods The FertiQoL questionnaire was conducted through an online-platform and consisted of 24 items derived from four subscales (mind-body, emotional, social, and relational), 10 treatment-related items, and two overall life and physical wellness items. Additionally demographic infertility-related characteristics were answered by the participants. Generalized Linear Models were performed to assess the association between FertiQoL scores and duration of infertility. Results are described by B coefficient and the p value. Main results and the role of chance A negative association between duration of infertility and FertiQoL scores were observed. With one unit increase in duration of infertility, the log of odds of having a positive perception about: (i) one’s own health decreases by -2.07 to -5.49, p < 0.001, (ii) one’s satisfaction with the quality of life decreases by -0.981 to -3.90, p < 0.001, (iii) ability to handle other life plans and goals while dealing with infertility decreases by -0.59 to -2.77, (iv) ability to deal with one's fertility issues decreases by-1.38 to -4.00, p < 0.001, (v) experience of envy feelings increases by 0.10 to 2.71, p < 0.001, (vi) experience oscillations of hope and hopelessness feelings increases by 0.25 to 0.97, p < 0.001, (vii) experience of social isolation due to infertility increases by 0.92 to 3.12, p < 0.001, (viii) loving to one's partner despite fertility problems decreased by -0.54 to -5.99 p < 0.001, (ix) feeling discomfort in social situations increases by 0.80 to 2.73, p < 0.001, (x) feeling of inferiority in relation to people who have children increases from 0.48 to 1.29, p < 0.001, (xi) feeling of anger due to infertility increases from -0.20 to -1.56, p < 0.001, and (xii) unpleasant effects of infertility treatment increases from 0.217 to 1.97, p < 0.001. Limitations, reasons for caution Lack of adequate opportunities to conduct face to face interview and lack of knowledge of the real state of the participants, concerning infertility or when involved in an assisted reproduction treatment (ART), knowledge of which treatment. Wider implications of the findings Long infertility duration is a significant risk factor affecting women's QoL and psychological health. It can be hypothesized that, besides the duration of infertility itself, repeated ART treatments related to longer infertility may compromise QoL, highlighting the importance of the psychological counseling for infertile patients, especially those with longer infertility. Trial registration number Not applicable