Purpose The purpose of this meta-analysis was to determine the effect of nurse-led diabetes self-management education (DSME) on blood glucose control and cardiovascular risk factors. Methods The electronic databases PubMed and ISIS Knowledge were searched for relevant randomized controlled studies published between 1999 and 2009. Effect size was calculated for change in A1C, blood pressure, and lipid levels using both fixed- and random-effects models. Subgroup analyses were performed on patient age, gender, diabetes type, baseline A1C, length of follow-up, and study setting. Results A total of 34 randomized controlled trials with a combined cohort size of 5993 patients was identified. Mean patient age was 52.8 years, 47% were male, and mean A1C at baseline was 8.5%. Mean change in A1C was a reduction by −0.70% for nurse-led DSME versus −0.21% with usual care (UC). This corresponded to an effect size of 0.506, using a random-effects model for nurse-led DSME versus UC. Effect size was significantly associated with patient age older than 65 years and with duration of follow-up. Nurse-led DSME was also associated with improvements in cardiovascular risk factors, particularly among male patients, among those with good glycemic control, and in studies conducted in the United States. Conclusions Nurse-led DSME is associated with improved glycemic control, demonstrating that programs are most effective among seniors and with follow-up periods of 1 to 6 months. Future programs tailored to the needs of patients younger than 65 years may improve the impact of DSME on blood glucose.