We used meta-analysis to synthesize current evidence regarding the effect of nasal continuous positive airway pressure (nCPAP) on road traffic accidents in patients with obstructive sleep apnea (OSA) as well as on their performance in driving simulator. The primary outcomes were real accidents, near miss accidents, and accident-related events in the driving simulator. Pooled odds ratios (ORs), incidence rate ratios (IRRs) and standardized mean differences (SMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. Furthermore, risk differences (RDs) and numbers needed to treat (NNTs) were estimated for real and near miss accidents. Meta-regression analysis was performed to examine the effect of moderator variables and publication bias was also evaluated. Ten studies on real accidents (1221 patients), five studies on near miss accidents (769 patients) and six studies on the performance in driving simulator (110 patients) were included. A statistically significant reduction in real accidents (OR = 0.21, 95% CI = 0.12–0.35, random effects model; IRR = 0.45, 95% CI = 0.34–0.59, fixed effects model) and near miss accidents (OR = 0.09, 95% CI = 0.04–0.21, random effects model; IRR = 0.23, 95% CI = 0.08–0.67, random effects model) was observed. Likewise, a significant reduction in accident-related events was observed in the driving simulator (SMD = −1.20, 95% CI = −1.75 to −0.64, random effects). The RD for real accidents was −0.22 (95% CI = −0.32 to −0.13, random effects), with NNT equal to five patients (95% CI = 3–8), whereas for near miss accidents the RD was −0.47 (95% CI = −0.69 to −0.25, random effects), with NNT equal to two patients (95% CI = 1–4). For near miss accidents, meta-regression analysis suggested that nCPAP seemed more effective among patients entering the studies with higher baseline accident rates. In conclusion, all three meta-analyses demonstrated a sizeable protective effect of nCPAP on road traffic accidents, both in real life and virtual environment.