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Background: Menstruation is a major physiological change in a woman's life, but lack of knowledge, poor practices, socio-cultural barriers, poor access to products and their improper disposal have significant consequences on health, dignity and well-being of women and adolescent girls. Objectives: This study aimed to assess the knowledge and practices related to menstrual health and hygiene amongst females of 10–49 years of age; explore the experiences and challenges of women during menstruation; and identify the key predictors of healthy menstrual health and hygiene. Methods: Using a cross-sectional study design, we adopted a mixed methods approach for data collection. For quantitative household survey, a total of 921 respondents were selected from three districts of Odisha. Qualitative findings through focus group discussions and in-depth interviews supplemented the survey findings and helped to identify the barriers affecting good menstrual practices. Epi data version 2.5 and R 4.2.2 was used for data entry and data analysis, respectively. Descriptive statistics was used to calculate proportion, mean and standard deviation; Chi square test was used to measure the association between categorical variables. Bivariate and multivariate logistics analyses were done to identify predictors of healthy menstrual health and hygiene. For qualitative data analysis, thematic analysis approach was adopted using software Atlas.ti 8. Results: For 74.3% respondents, mothers were the primary source of information; about 61% respondents were using sanitary pad. The mean age at menarche was 12.9 years and almost 46% of respondents did not receive any information about menstruation before menarche. Lower age and education up to higher secondary level or above had statistically significant associations with the knowledge about menstruation. Age, caste, respondent's education, mother's education, sanitation facility, availability of water, accessibility and affordability for sanitary pads were found to be strongly associated with good menstrual hygiene practices. Conclusion: Traditional beliefs regarding menstruation still persists at the community level. Educating mothers, increasing awareness about safe menstrual hygiene, providing adequate water and sanitation facilities and ensuring proper disposal of menstruation products need priority attention. [ABSTRACT FROM AUTHOR]