Blood glucose (BG) monitoring (BGM) is an important component of diabetes management. New wireless technologies may facilitate BGM and help to optimize glycemic control. We evaluated an integrated wireless approach with and without a motivational game in youth with diabetes. Forty youth, 8-18 years old, each received a handheld device fitted with a wireless modem and diabetes data management software, plus a wireless-enabled BG monitor. Half were randomized to receive the new technologies along with an integrated motivational game in which the participants would guess a BG level following collection of three earlier readings (Game Group). BG data, insulin doses, and carbohydrate intake were displayed graphically prior to the glucose estimation. The other group received the new technologies alone (Control Group). Both groups were instructed to perform BGM four times daily and transmit their data to a central server via the wireless modem. Feasibility of implementation and outcomes were ascertained after 4 weeks. Ninety-three percent of participants successfully transmitted their data wirelessly to the server. The Game Group transmitted significantly more glucose values than the Control Group (P < 0.001). The Game Group also had significantly less hyperglycemia (glucose >/=13.9 mmol/L or >/=250 mg/dL) than the Control Group (P < 0.001). Youth in the Game Group displayed a significant increase in diabetes knowledge over the 4-week trial (P < 0.005). Finally, there was a trend for more youth in the Game Group to maintain hemoglobin A1C values </=8% (P = 0.06). Thus a pediatric population with diabetes can successfully implement new technologies to facilitate BGM. Use of a motivational game appears to increase the frequency of monitoring, reduce the frequency of hyperglycemia, and improve diabetes knowledge, and may help to optimize glycemic control.