We aimed to compare rates of illicit drug-related hospitalisations in HIV-negative (HIV-ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11-16, F18, F19), drug poisoning (T40-T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV-ve cohort [SIR 4.75 (95 % CI 3.30-6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92-5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01-3.46)], poly-drug use [IRR 2.17 (1.07-4.38)] and cannabis use [low use-IRR 1.95 (1.01-3.77), high use-IRR 2.58 (1.29-5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07-9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61-9.66), IRR 4.43(1.04-18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use.