Few studies have examined the effect of working night shift and long distance commuting. We examined the association between several sleep related and demographic variables, commuting distance, night work and use of mobile phones on driving performance. We used a prospective design to recruit participants and conducted a telephone survey (n=649). The survey collected demographic and journey details, work and sleep history and driving performance concerning the day the participant was recruited. Participants also completed the Karolinska Sleepiness Scale and the Epworth Sleepiness Scale. Night workers reported significantly more sleepiness, shorter sleep duration and commuting longer distances. Seven variables were significant predictors of lane crossing. The strongest predictor was acute sleepiness (OR = 5.25, CI, 1.42 – 19.49, p < 0.01) followed by driving ≥ 150kms (OR = 3.61, CI, 1.66 – 7.81, p < 0.001), obtaining less than 10 hours sleep in the previous 48 hours (OR = 2.58, CI, 1.03 – 6.46, p < 0.05), driving after night shift (OR = 2.19, CI, 1.24 – 3.88, p < 0.001), being < 43 years old (OR = 1.95, CI, 1.11 – 3.41, p < 0.05) and using mobile phones during the journey (OR = 1.90, CI, 1.10 – 3.27, p < 0.05). Sleep related variables, long-distance commuting and night work have a major impact on lane crossing. Several interventions should be considered to reduce the level of sleepiness in night workers.