Chronic respiratory insufficiency (CRI) is associated with nocturnal hypoventilation. Treatment with noninvasive mechanical ventilation (NIMV) performed overnight relieves symptoms of hypoventilation and improves daytime blood gases in CRI. In order to test whether the efficacy of NIMV depends on it being applied during sleep, we conducted a prospective case-controlled study comparing daytime mechanical ventilation (dMV) in awake patients with nocturnal mechanical ventilation (nMV) given in equal quantities. We enrolled 34 clinically stable patients (age 56.1+/-12.1 yrs, 20 females, 14 males) with CRI due to restrictive lung and chest wall disorders and neuromuscular disease. Using a prospective case-control design, matched subjects were allocated alternately to dMV and nMV. After 1 month of NIMV there was considerable symptomatic improvement in both dMV and nMV patients. There were no significant differences between groups in the improvement in daytime arterial carbon dioxide tension (Pa,CO2) (dMV from 7.5+/-0.6 to 5.7+/-0.6 kPa; nMV from 7.2+/-0.5 to 5.8+/-0.5 kPa, p<0.0001) and during the unassisted spontaneous night-time ventilation in terms of transcutaneous Pa,CO2 (dMV from 8.4+/-1.2 to 6.6+/-0.7 kPa; nMV from 8.2+/-1.2 to 6.8+/-0.5 kPa, p<0.0001). We conclude that in many respects, when compared to nocturnal mechanical ventilation, daytime mechanical ventilation in awake patients is equally effective at reversing chronic respiratory insufficiency. Since long-term safety issues were not addressed in this study, we recommend that nocturnal mechanical ventilation should remain the modality of choice for noninvasive mechanical ventilation.