The aim of this study was to compare the efficacy and safety of salmeterol vs theophylline in asthma management using meta-analysis of clinical trials. Nine clinical studies, containing a total of 1330 patients, met meta-analysis inclusion criteria: randomized, controlled study, minimum 2-week treatment duration with either salmeterol or theophylline. The main outcome measurements were morning and evening peak expiratory flow rate (PEFR), morning and evening symptom scores, use of salbutamol as rescue medication, and withdrawal from treatment for any cause. During the second week of treatment, salmeterol patients had a 10 l min-1 greater increase in mean morning PEFR from baseline than theophylline patients (P < 0.001). Similarly, in the second week, the increase in mean evening PEFR from baseline observed with salmeterol was significantly greater (P < 0.01) than that observed with theophylline. Salmeterol also produced a significantly greater increase in mean morning and evening PEFR than theophylline at weeks 3 and 4. Patients receiving salmeterol were free from daytime symptoms for a mean of 51% of days in the second week compared to 39% for theophylline patients (P < 0.001). Salmeterol patients experienced a mean of 63% symptom-free nights compared to 52% for theophylline patients (P < 0.001). Rescue medication with salbutamol was not required on 49% of days for salmeterol patients and 34% of days for theophylline patients. All results were maintained in the third and fourth weeks of treatment. Withdrawal and incidence of adverse events leading to withdrawal were significantly less frequent in patients receiving salmeterol (P < 0.001). Thus, this meta-analysis suggests that salmeterol has a superior safety and efficacy profile to theophylline in the management of symptoms of chronic asthma.