BACKGROUND A combination of salmeterol and fluticasone propionate (SAL/FP) has been shown to be effective in the treatment of asthma. We compared the efficacy and tolerability of SAL/FP (50/250 μg) with fluticasone propionate (FP) 250 μg administrated twice daily for 2 weeks in treating patients with mild to moderate asthma. METHODS This was a randomized, double-blind study in adult patients with symptomatic asthma that was not controlled by 1000 μg/d inhaled corticosteroids (ICS) alone. 48 asthmatics were randomized to receive 2 inhalations of SAL/FP 50/250 μg bis in die (BID) or 2 inhalations of FP 250 μg BID, both delivered via Accuhaler device, for 2 weeks. The primary objective was the mean change from baseline in the mean morning peak expiratory flow (PEF) over the two week period. Other parameters included lung function, daily asthma symptom scores, evening PEF, percentage of days free of rescue medication use and daily rescue medication use. Tolerability was assessed by adverse events spontaneously elicited at clinic visits. RESULTS 46 patients provided evaluable efficacy for analysis. The morning PEF improved significantly throughout the two weeks of treatment compared with baseline in the SAL/FP group. Mean morning PEF was 23.0 L/min higher in SAL/FP group than in FP group (p = 0.013). The change of forced expiratory volume in one second (FEV1) from baseline was greater in SAL/FP group compared to FP group (p = 0.048). There were similar effects on day-time and night-time symptom scores, percentage symptom free days and nights and usage of salbutamol. 70.8% of the patients receiving SAL/FP were satisfied with the treatment, while only 26.1% of patients receiving FP alone were (p = 0.020). No death or acute exacerbation occurred. CONCLUSIONS SAL/FP 50/250 μg was safe and effective, and had a high level of patient satisfaction resulting in significantly greater increases in morning PEF and FEV1 compared to the use of FP 250 μg alone.