BACKGROUND: About one third of patients fail their first CPAP trial due to several factors. Despite its clinical importance, data on the success of CPAP re-initiation are scarce. METHODS: Of the 6,231 patients referred to our sleep unit for sleep apnea, we included 224 subjects referred for re-initiation of CPAP therapy (re-CPAP). The control group consisted of 228 CPAP-naïve subjects referred for CPAP initiation. Data on subject characteristics, sleep study, and CPAP outcome were collected. RESULTS: The re-CPAP group had more severe apnea than the control group. After at least 1 y of CPAP therapy, 52% of the re-CPAP group stayed on therapy; this was significantly lower than the 67% adherence for the control group (P 5 .001). No gender difference was observed in the control group (P 5 .12), whereas women in the re-CPAP group remained on therapy significantly less than men (P 5 .002). CONCLUSIONS: The percentage of subjects who stayed on CPAP therapy after 1 y was significantly reduced when CPAP was re-initiated compared to the control group. CPAP acceptance after re-initiation was higher among men than women. Further studies are necessary to explain this gender difference.