Purpose: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. Methods: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan–Meier estimators using observational data on adult HIV-infected patients and background population. Results: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3–11.5), corresponding to 22.3% (95% CI 18.5–26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0–44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6–8.2). No increase in LE with later calendar period of diagnosis was observed. Conclusions: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6–12.2) and 9.9 years (95% CI 7.6–12.1) for the periods 2005–2010 and 2014–2016, respectively).