Background. Educational interventions with multifaceted approach have proven effective to improve adherence to the therapeutic regimen in people with chronic diseases. This study sought to evaluate the efficacy of the nursing intervention “Teaching: Individual” compared with usual care to increase adherence to therapeutic regimen and to analyze the impact of nursing interventions to decrease systolic blood pressure (SBP) and glycosylated hemoglobin (HbA1c) levels in people with hypertension and/or type-2 diabetes mellitus. Methods. This was a two-arm parallel randomized clinical trial in 200 patients from primary care programs with arterial hypertension and type-2 diabetes. The intervention was designed with a multifaceted approach and conducted individually in six sessions. For statistical analysis of SBP, a linear marginal model was used with an exchangeable correlation matrix for repeated measures, and for treatment adherence as well as generalized HbA1c estimating equations repeated measures were used with an unstructured correlation matrix, using all available data. All analyses were conducted in STATA software version 15.0. Values of p <0.05 were considered statistically significant. Results. After six months the follow up score adherence to the therapeutic regimen was higher in the “Teaching: Individual” group compared with the usual care group with a difference in the median of 0.87 points (95% CI: 0.30 to 1.44). The difference in the median of SBP between the groups was -3.79 mmHg (95% CI: -6.85 to -0.73), in favor of the group intervened. The difference in the median of HbA1c was -0.16% (95% CI: -0.41 to 0.09). The effect was not maintained at 12 months of follow up in none of the variables of interest. Conclusions. As well as in other contexts, this study determined that educational interventions with multifaceted approach leaded by nursing are effective in improving therapeutic adherence and control of tension figures in users of primary care programs with high blood pressure and type-2 diabetes. Trial Registration: ENURSIN was registered in ClinicalTrials.gov (NCT02758275) on 27 April 2016, protocol number 01. Keywords: Nursing Process; Diabetes Mellitus, Type 2; Hypertension, Patient Education as a Topic, Blood Pressure Monitoring, Ambulatory; Treatment Adherence and Compliance; Glycated Hemoglobin A.