Background Sleep disturbances among medical staff are common serious entities with devastating consequences. Numerous studies have analyzed the effects of residency on the quality of sleep of the medical trainees in various specialties, but only few studies were conducted in Egypt. Results One hundred fifty medical residents from various medical and surgical specialties who work in the hospitals of Ain Shams University, Egypt, agreed to participate in our study. Sociodemographic and work-related data were collected by a semi-structured sheet. Sleep quality was assessed by self-administered questionnaire—Pittsburgh Sleep Quality Index (PSQI). According to the PSQI, 96.7% of the residents had poor sleep quality with mean PSQI score of 10.4 ± 2.5. No statistically significant difference was detected among the different specialties. Poorer sleep quality was more frequent among senior residents who spent longer duration in residency. The number of hours of sleep before residency and the number of days off during residency were the main predictors of total PSQI score and determinants of sleep quality Conclusions Poor sleep quality is highly prevalent among medical residents and is associated with work-related factors. It is necessary to consider residents’ sleep estate and conduct more analyses to diagnose, treat, and improve their sleep quality.