OBJECTIVE: To investigated the effectiveness of an adherence intervention (AIMS) designed to fit HIV-clinics' routine care procedures. DESIGN: Through block randomization, patients were allocated to the intervention or control group. The study included 2 months baseline measurement, 3 months intervention, and 4 months follow-up. HIV-nurses delivered a minimal intervention ("adherence sustaining") to patients scoring >95% adherence at baseline, and an intensive intervention ("adherence improving") to patients with <95% adherence. Control participants received high-quality usual care. MAIN OUTCOME MEASURES: Electronically monitored adherence and viral load. RESULTS: 133 patients were included (67 control, 66 intervention), 60% had <95% adherence at baseline, and 87% (116/133) completed the trial. Intent-to-treat analyses showed that adherence improved significantly in the complete intervention sample. Subgroup analyses showed that this effect was caused by participants scoring <95% at baseline (mean difference = 15.20%; p < .001). These effects remained stable during follow-up. The number of patients with an undetectable viral load increased in the intervention group compared to the control group (OR = 2.96, p < .05). Treatments effects on viral load were mediated by the improvements in adherence. CONCLUSIONS: The AIMS-intervention was effective and can be integrated in routine clinical care for HIV-infected patients. Future research should study its (cost)effectiveness among more heterogeneous samples and in settings with variable levels of standard care.