BACKGROUND: Trials have shown total diet replacement (TDR) programmes are safe and effective for weight loss in primary care. However, it is not clear whether participant characteristics affect uptake, attendance, or effectiveness of the programme. METHODS: We used data from 272 trial participants who were invited to participate in a clinical weight loss trial via a letter from their GP. We used a Cochran-Mantel-Haenszel analysis to assess whether accepting an invitation to participate in the trial differed by gender, age, BMI, social deprivation, and the presence of a diagnosis of type 2 diabetes or hypertension. We used mixed generalised linear modelling to examine whether participants' age, gender, or social deprivation based on area of residence were associated with weight change at 12 months. RESULTS: Men were less likely to enrol than women (RR 0.59 [95% CI 0.47, 0.74]), and people from the middle and highest BMI tertile were more likely to enrol than those from the lowest tertile (RR 2.88 [95% CI 1.97, 4.22] and RR 4.38 [95% CI 3.05, 6.07], respectively). Patients from practices located in most deprived and intermediate deprived tertiles were more likely to enrol compared with those in the least deprived tertile (RR 1.84 [95% CI 1.81, 2.59] and RR 1.68 [95% CI 1.18, 2.85], respectively). There was no evidence that age or a pre-existing diagnosis of type 2 diabetes (RR 1.10 [95% CI 0.81, 1.50]) or hypertension (RR 0.81 [95% CI 0.62, 1.04]) affected enrolment. In the TDR group, 13% of participants were low engagers, 8% engaged with the weight loss phase only, and 79% engaged in both weight loss and weight maintenance phases of the programme. Those who engaged in the entire programme lost most weight. Subgroup analyses suggested that older participants and those with a higher baseline BMI lost more weight at 1 year than their comparators. CONCLUSION: Despite some heterogeneity in the uptake and outcomes of the programme, if the results of this trial are replicated in routine practice, there is no evidence that TDR weight loss programmes would increase inequity. TRIAL REGISTRATION: The DROPLET trial was prospectively registered on ISRCTN registry (ISRCTN75092026).