Introduction: Patients with mild to moderate obstructive sleep apnoea (OSA) commonly suffer excessive daytime sleepiness. Continuous positive airway pressure (CPAP) has limited effectiveness in reducing sleepiness in milder OSA. Modafinil is a wake-promoting drug licensed to treat residual sleepiness in CPAP-treated OSA. We hypothesised that modafinil may effectively treat sleepiness in untreated mild to moderate OSA. Methods: Untreated sleepy men with mild to moderate OSA (age 18-70, apnoea-hypopnoea index (AHI) 5-30/h, Epworth Sleepiness Scale (ESS) ≥10) were randomised to receive 200 mg modafinil or matching placebo daily for 2 weeks before crossing over to the alternative treatment after a minimum 2-week washout. Mixed model analysis of variance was used to compare the changes on modafinil to placebo while classifying all randomised patients as random factors. Results: 32 patients were randomised (mean (SD) AHI 13 (6.4)/h, age 47 (10.7) years, ESS 13.6 (3.3), body mass index 28.2 (3.6) kg/m2), 29 of whom (91%) completed the trial. The primary outcome (ESS) improved more on modafinil than placebo (3.6 points, 95% CI 1.3 to 5.8, p=0.003) and the secondary outcome (40-min driving simulator performance) also improved more on modafinil than placebo (steering deviation 4.7 cm, 95% CI 0.8 to 8.5, p=0.018). Psychomotor Vigilance Task reciprocal reaction time improved significantly over placebo (0.15 (1/ms), 95% CI 0.03 to 0.27, p=0.016). Improvements on the Functional Outcomes of Sleep Questionnaire were not significant (5.3 points over placebo, 95% CI -1 to 11.6, p=0.093). Conclusions: Modafinil significantly improved subjective sleepiness in patients with untreated mild to moderate OSA. The size of this effect is clinically relevant at 3-4 ESS points of improvement compared with only 1-2 points in CPAP clinical trials. Driving simulator performance and reaction time also improved on modafinil.