Evidence suggests that a low-glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight-loss maintenance. It consisted of a weight-loss phase and a 4-month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2–7.1) % body weight, subjects were randomized to a high-glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 ± 9.4; LGI group: 49.7 ± 5.7, P < 0.001) and glycemic load (HGI group: 136.8 ± 56.3; LGI group: 89.7 ± 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 ± 1.9 kg; LGI group: −0.7 ± 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.