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SummaryBackgroundHuman immunodeficiency virus (HIV) infection has been reported to be a risk factor for porphyria cutanea tarda (PCT).PurposeTo assess the strength of the association between HIV infection and PCT in a large hospital setting.MethodsAll patients (N = 210) diagnosed of PCT between 1990 and 2014 were retrospectively investigated for HIV infection and co‐precipitating factors. High‐performance liquid chromatography was used to assess the appearance of pre‐PCT urinary porphyrin abnormalities among a group (N = 22) of HIV‐infected patients without PCT using the urine of patients co‐infected with hepatitis C virus (HCV) without PCT for comparison.ResultsTwenty‐six HIV‐infected patients (19 males and seven females) were diagnosed of PCT. During the same interval of time, ~8000 different patients infected with HIV were attended in the hospital of infectious diseases department. Examination of risk factors showed that 25 out of 26 of the PCT patients with HIV were co‐infected with HCV. No chromatographic abnormalities were found in the urine of non‐PCT‐HIV‐infected patients, whereas 39% co‐infected patients showed urinary porphyrin abnormalities.ConclusionsIn our large hospital series, the appearance of PCT among HIV‐infected patients is low (<1%) and most present co‐infection with HCV. Therefore, in most HIV‐infected patients with PCT, hepatitis C and not HIV may induce uroporphyrinogen decarboxylase deficiency.