Summary Background Exhaled NO (FENO ) is a useful biomarker for the monitoring of asthma control and response to therapy. However, there is a lack of data on FENO levels and their interpretation in Primary Care asthma population depending on their treatment and smoking habit. Besides, the majority of current FENO tests have been done by stationary chemiluminescence analysers whose use is limited to research laboratories. Methods FENO measurements by the novel hand-held NO monitoring device (NIOX MINO® ) were made in 96 asthma patients (32 males, mean age 53 ± 12) at five local General Practices during their scheduled 15–20 min visits for lung function assessment. Results Success rate was 78% and the intra-subject coefficient of variation was 8.7%. Inhaled corticosteroid treatment had an overall reducing effect on the FENO value (30.5 19.8–49.8) vs. patients not on the ICS (26.5 19–94) ( p < 0.044). FENO levels in the ICS treated current or ex-smokers group of patients were still significantly above the normal values ( p < 0.0001). FENO levels were similar in patients receiving ICS whether there were current, ex-smokers or non-smokers. The highest FENO levels (94 15.8–151) were found in asthmatic current smokers and not receiving treatment with ICS. The most “normalised” FENO levels (35.3 13.5–35.3) were seen in ex-smokers. Conclusions FENO measurements performed with a new hand-held monitoring device are reproducible and feasible in General Practice in the majority of patients of different ages and asthma severities. A high percentage of patients with different severities of asthma and regardless of their treatment with ICS and current smoking habit (current and/or ex-smokers) had highly elevated FENO values, suggesting that their current therapy was possibly insufficient to control the underlying degree of airway inflammation and asthma symptoms.