OBJECTIVE: To quantify and characterize missed opportunities for earlier HIV diagnosis in patients diagnosed with advanced HIV. DESIGN: A retrospective observational cohort study. SETTING: A central tertiary medical center in Israel. MEASURES: The proportion of patients with advanced HIV, the proportion of missed opportunities to diagnose them earlier, and the rate of clinical indicator diseases (CIDs) in those patients RESULTS: Between 2010-2015, 356 patients were diagnosed with HIV, 118 (33.4 %) were diagnosed late, 57 (16%) with advanced HIV disease. Old age (OR=1.45 [95% CI 1.16-1.74]) and being heterosexual (OR=2.65 [95% CI 1.21-5.78]) were significant risk factors for being diagnosed late. All patients with advanced disease had at least one CID that did not lead to an HIV test in the 5 years prior to AIDS diagnosis. The median time between CID and AIDS diagnosis was 24 month (IQR 10-30). 60% of CIDs were missed by a general practitioner and 40% by a specialist. CONCLUSIONS: Missed opportunities to early diagnosis of HIV occur both in primary and secondary care. Lack of national guidelines, lack of knowledge regarding CIDs and communication barriers with patients may contribute to HIV late diagnosis. 'Strengths and limitations of this study' This study shows for the first time rate and reasons for missed opportunities to diagnose HIV in a low prevalence country like Israel. This study may shed light on the reasons why primary care physicians or specialists are missing to diagnose HIV earlier. Nonexistence of clear national guidelines for HIV testing and ignoring HIV clinically indicator diseases are major reasons for missed diagnosis of HIV. This study was carried out in one center and may not reflect the picture in the all country; Also, the total number of patients is low and this may limit generability of the study