Objective: Rising incidence of acquired multidrug-resistant tuberculosis (MDR-TB) in South Africa suggests low knowledge and implementation of infection prevention and control strategies in household and congregate settings. This study contributes to the under-researched area of non-biomedical responses to sub-adherence to treatment. Design: The study utilises a quasi-ethnographic qualitative case study of 10 women aged 18 to 34 years to understand their treatment adherence behaviours through the lens of their sex, gender, age, cultural beliefs and socio-economic status. Setting: This study investigated reasons for young women's sub-optimal adherence to treatment for acquired MDR-TB in eThekwini Metro, KwaZulu-Natal province, South Africa, which records high burdens of tuberculosis (TB), MDR-TB and HIV. Methods: Primary data were collected from 20 participants who were selected through criterion, purposive and snowball sampling. Data were gathered through focus group discussions with women being treated for transmitted MDR-TB and key informant interviews with their family members, health workers and KwaZulu-Natal Provincial Department of Health personnel. Results: Anti-MDR-TB treatment affects women's sexuality, intimate relationships, family planning intentions and reproductive health. Some vulnerable women struggle to persevere on noxious and lengthy treatment regimes that affect their reproductive and psychological health. Women may skip doses or abandon treatment when high pill burdens and adverse events make intimate and sexual relations with male partners, on whom they may depend for their livelihoods, difficult. Conclusion: It is important to consider the effects of lengthy treatment on young people's social and sexual lives and self-esteem when (re)designing MDR-TB counselling approaches. This paper advances an evidence-based treatment education and counselling strategy to contribute to improving MDR-TB treatment adherence and success.