Objective: The objective of this study was to determine if the preoperative use of antifungal therapy positively influences clinical outcome in patients with Aspergillus brain abscess. Methods: We studied 25 patients with confirmed diagnosis of cerebral aspergillosis. We compared baseline characteristics and outcomes of patients treated with either amphotericin B or itraconazole either pre-operatively (n = 11) or post-operatively (n = 14) at a tertiary care hospital in Karachi. Results: Twenty-five patients were included in the study. Cerebral aspergillosis was largely a disease of immune competent people (80%). Baseline clinical characteristics between the two treatment groups were comparable i.e., age (P > 0.896), gender (P > 0.999), coma at presentation (P > 0.999), immunosuppression (P > 0.623), number of abscesses (P > 0.999) and interval between presentation and surgery (P > 0.447). Overall mortality was 40%. The overall outcome was significantly better (P < 0.001) in patients treated with antifungal therapy before surgery. All 11 patients who received antifungal therapy before surgery survived, but only preoperative itraconazole treatment was statistically associated with an improved survival compared to delayed treatment. Conclusion: Cerebral aspergillosis was largely a disease of immune competent people (80%). Overall mortality was 40%. The outcome was significantly better in patients treated with antifungal therapy (especially itraconazole) before surgery suggesting a possible beneficial effect of pre-surgical treatment with antifungal therapy.