There is limited evidence detailing the cost-effectiveness of psoriasis treatments in the Asian region. Therefore, this study is aimed to evaluate the cost-effectiveness of 3 psoriasis treatments tailored for moderate to severe psoriasis, namely topical and phototherapy (TP), topical and systemic (TS), and topical and biologic (TB) regimens, respectively.This has been achieved by the participation of a prospective cohort involving a total of 90 moderate to severe psoriasis patients, which has been conducted at 5 public hospitals in Malaysia. The main outcome measures have been evaluated via cost and effectiveness psoriasis area severity index (PASI)-75 and/or body surface area (BSA) <5 and/or dermatology life quality index (DLQI) ≤5), estimated from the societal perspective over a 6-months duration. All costs are based on 2015's recorded Malaysian Ringgit (RM) currency.Consequently, TS has been found to be the most cost-effective treatment with the lowest cost/PASI-75/and/or BSA <5 and/or DLQI ≤5, valued at RM9034.56 (US$2582.55). This is followed by TP, which is valued at RM28 080.71 (US$8026.93) and TB, valued at RM54 287.02 (US$15 518.06). Furthermore, one-way sensitivity analysis has highlighted the cost of medication as the most sensitive parameter.Thus, the input from this study is helpful for policy-makers in determining the first line treatment for moderate to severe psoriasis with consideration of the costs and its effectiveness in Malaysia. This will consequently allow hospitals to justify and provide the essential resources for further research and development, as well as the adoption of better treatment options.