Introduction: Palmoplantar pustular psoriasis (PPPP) is a debilitating inflammatory skin disorder of the palms and soles that poses a high burden on affected patients. Satisfactory treatment response is rarely achieved using current treatment options, little is known about the potential benefit of the PDE4 inhibitor apremilast in the treatment of refractory PPPP patients. We aimed to evaluate the use of apremilast in PPPP patients. Patients and Methods: Six patients, four with severe physician global assessment (PGA) = 3 on a scale of 0–4 and two with very severe (PGA = 4) treatment-refractory PPPP [mean age (years ± SD): 56.2 ± 15.6], were included in this study. Five patients had concomitant psoriatic arthritis (PsA). Prior to apremilast administration, topical corticosteroids, psoralen-UVA and multiple systemic oral and biologic anti-inflammatory treatments were insufficient to improve their skin condition or had to be discontinued due to adverse events. Apremilast (titrated to a maintenance dose of 30 mg 2x/d) was commenced in all patients with clinical follow-up over 18 months. Results: Within the first 4 weeks of treatment, each patient's symptoms improved as assessed by PGA score. At 3 months, four patients had a mild PGA score and two were cleared from PPPP. After 18 months of follow-up, three patients improved from PGA = 3 to PGA = 1 and one patient from PGA = 4 to PGA = 1. Two patients discontinued treatment, one due to a lack of efficacy against PsA and the other to a desire to have a child. However, both patients recorded improvements before discontinuing treatment. Conclusion: Apremilast may be a promising treatment option for refractory and severely affected PPPP patients. Our observation, however, requires further validation.