Objective. To evaluate the relationship that tiredness and sleepiness in bus drivers have to road accidents in Peru. Information from various countries indicates that driver sleepiness plays an important role in road accidents. However, there is only limited information on this subject in Peru. Methods. Using a supervised, pretested survey, a cross-sectional observational and comparative study was carried out with 238 bus drivers who drive on the Northern Pan American Highway of Peru. To determine the relationship between variables the chisquare test was used, along with the Pearson correlation coefficient. The level of significance was set at P < 0.05. The variables analyzed were: tiredness, sleepiness, hours of driving per day, daily hours of sleep, body mass index, snoring, sleep apnea, and either having had or almost having had an accident while driving. Results. Of the 238 drivers, all of them were men, 45% said they had had or nearly had had an accident while driving, 55% slept less than 6 hours per day, 31% had slept less than 6 hours in the 24 hours before answering the survey, and 80% were in the habit of driving more than 5 hours without stopping. Of the drivers, 56% of them reported being tired at least some of the time while driving; of this group, 65% of them reported being tired during the early morning. Seventy-six drivers (32%) said that while they were driving their eyes had fallen shut. In terms of where they slept, 194 of the drivers (81%) said they always slept in the lower luggage compartment of the bus while another driver was driving the bus or when the bus was parked in the bus terminal. The steps that drivers took to avoid falling asleep while driving included: wetting the face with water, eating fruit, opening the window of the driver's compartment, drinking coffee, listening to music, smoking, chewing coca leaves, and drinking alcohol mixed with coca leaves. In the opinion of 55% of the drivers, the leading cause of road accidents is tiredness. Accidents and near-accidents while driving occurred mainly between midnight and 6 a.m. Having an accident or a near-accident was strongly associated with tiredness and with having the eyes drop shut while driving (P < 0.0005). Conclusions. Tiredness and sleepiness while driving were common among the bus drivers, with various possible causes: acute and chronic sleep deprivation, irregular schedule changes, and sleep disorders due to the drivers' working conditions. Our results support the hypothesis that fatigue and sleepiness among bus drivers are related to road accidents.