Evidence for superior outcome by adhering to therapy guidelines is imperative to their acceptance and adaptation for the optimal management of disease variants. Objective: Comparative study of prospective outcomes in simultaneous consideration of independent variables in groups of 150 patients of plaque psoriasis either treated adhering to or in digression of standard guidelines. Methods: The psoriasis area severity index (PASI) and the dermatology life quality index (DLQI), prior to and after three months of uninterrupted therapy were examined in treatment groups among 150 patients. Recovery rates of 75% or more in PASI were compared. Independent variables were also examined for their bearing on the outcome. Results: The vast majority was early onset disease phenotype. All three treatment regimens when administered in adherence to the guidelines yielded significantly superior rates of defined recovery both in PASI and DLQI. Compromise of the therapeutic outcome appeared in high stress profiles, obesity, female sex and alcohol, tobacco or smoking habit. Conclusion: Conventional drug therapy of plaque psoriasis yields superior outcome by adhering to the consensus guidelines. Psychiatric address to stress must be integral and special considerations for phenotypic/syndromic variants is emphasized for effective therapy of psoriasis.