Consultation–liaison psychiatry (CLP) manages psychiatric care for patients admitted to a general hospital (GH) for somatic reasons. We evaluated patterns in psychiatric morbidity, reasons for referral and diagnostic concordance between referring doctors and CL psychiatrists. Referrals over the course of 20 years (2000–2019) made by the CLP Service at Modena GH (Italy) were retrospectively analyzed. Cohen’s kappa statistics were used to estimate the agreement between the diagnoses made by CL psychiatrist and the diagnoses considered by the referring doctors. The analyses covered 18,888 referrals. The most common referral reason was suspicion of depression (n = 4937; 32.3%), followed by agitation (n = 1534; 10.0%). Psychiatric diagnoses were established for 13,883 (73.8%) referrals. Fair agreement was found for depressive disorders (kappa = 0.281) and for delirium (kappa = 0.342), which increased for anxiety comorbid depression (kappa = 0.305) and hyperkinetic delirium (kappa = 0.504). Moderate agreement was found for alcohol or substance abuse (kappa = 0.574). Referring doctors correctly recognized psychiatric conditions due to their exogenous etiology or clear clinical signs; in addition, the presence of positive symptoms (such as panic or agitation) increased diagnostic concordance. Close daily collaboration between CL psychiatrists and GH doctors lead to improvements in the ability to properly detect comorbid psychiatric conditions.