Background: Health-care workers (HCWs) and professionals working in the pharmaceutical industry are at risk of developing occupational allergic contact dermatitis (OACD) from systemic drugs (or drug intermediates). Objectives: To study demographic characteristics and identify systemic drugs responsible for OACD in patients investigated for contact allergy during the period 2001-2019. Methods: In the study period, 9780 patients were patch tested with the European baseline series, sometimes with additional series, and other relevant potential allergens. All patients with a positive patch-test reaction to systemic medication exposed to at work were included for further analysis. Results: Of 1248 HCWs examined in our clinic, 201 suffered from OACD. In 26 (13%) dermatitis was caused by skin contact with a systemic drug: 19 nurses, five chemists working in the pharmaceutical industry, one physician, and one veterinarian. In total, 45 positive patch-test reactions to 20 different systemic drugs were found, with tetrazepam (n = 11), ranitidine hydrochloride (n = 5), and zolpidem (n = 4) being the most frequent. Three pharmaceutical chemists were sensitized to a drug intermediate. The lesions were mostly localized on the hands, but often also on the face, as airborne dermatitis. Conclusion: As much as 13% of OACD in HCWs, diagnosed in our tertiary referral center, was attributable to systemic drugs, most frequently in nurses.