Background: The treatment of penetrating head injuries and depressed skull fracture has shown a gradual change over the past decades. A proper debridement and closure of scalp wounds and dural tears have been shown to decrease infection and mortality rate of compound skull fractures. This study has been designed to determine the frequency of infection in early versus late surgery of compound depressed skull fractures in adults.Methods: A total of 226 (113 in each group) patients with compound depressed skull fracture were taken. Group A was managed by early surgery while group B underwent late surgery. Data were entered and analyzed using computer program SPSS version 18.Results: Out of these 226 study cases, 143(63.3%) were male, while 83 (36.7%) were females. The mean age of study cases was 37.50±10.58. The mean duration of presentation at the hospital was 6.76±2.41 hours. Roadside accident was noted to be a major etiological factor, i.e. 132 (58.4%) presented with the history of roadside accident. Base of the skull was a major site of wound, i.e. 79 (35.0%). The mean size of the wound was 13.79±3.49cm. Wound infection was seen in 51 (22.56%) of present study cases. Wound infection in group A was seen in 11 (9.7%) out of 113 patients while in group B it was 40 (35.4%) out of 113 patients (p=0.000).Conclusions: The findings of the current study have indicated that early surgery among the targeted population is associated with significantly less frequent wound infection.