Meal replacement Severely Energy-Restricted Diets (SERDs) produce ≥ 10% loss of body mass when followed for 6 weeks or longer in people with class III obesity (BMI ≥ 40 kg/m2). The efficacy of SERDs continues to be questioned by healthcare professionals, with concerns about poor dietary adherence. This study explored facilitators and barriers to dietary adherence and program attrition among people with class III obesity who had attempted or completed a SERD in a specialised weight loss clinic. Participants who commenced a SERD between January 2016 to May 2018 were invited to participate. Semi-structured in-depth interviews were conducted from September to October 2018 with 20 participants (12 women and 8 men). Weight change and recounted events were validated using the participants' medical records. Data were analysed by thematic analysis using line-by-line inductive coding. The mean age ± SD of participants was 51.2 ± 11.3 years, with mean ± SD BMI at baseline 63.7 ± 12.6 kg/m2. Five themes emerged from participants' recounts that were perceived to facilitate dietary adherence: (1.1) SERD program group counselling and psychoeducation sessions, (1.2) emotionally supportive clinical staff and social networks that accommodated and championed change in dietary behaviours, (1.3) awareness of eating behaviours and the relationship between these and progression of disease, (1.4) a resilient mindset, and (1.5) dietary simplicity, planning and self-monitoring. There were five themes on factors perceived to be barriers to adherence, namely: (2.1) product unpalatability, (2.2) unrealistic weight loss expectations, (2.3) poor program accessibility, (2.4) unforeseeable circumstances and (2.5) externalised weight-related stigma. This study highlights opportunities where SERD programs can be optimised to facilitate dietary adherence and reduce barriers, thus potentially improving weight loss outcomes with such programs. Prior to the commencement of a SERD program, healthcare professionals facilitating such programs could benefit from reviewing participants to identify common barriers. This includes identifying the presence of product palatability issues, unrealistic weight loss expectations, socio-economic disadvantage, and behaviour impacting experiences of externalised weight-related stigma.