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Summary Background There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. Objectives To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. Methods All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. Results There was a significant benefit in favour of active treatments against vehicle, SWMD: -1·06 (95% confidence interval [CI]: -1·26 to -0·86), approximately a 2-point improvement on a 12-point TSS after 6–8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: -1·51 (95% CI: -1·76 to -1·25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0·42 (95% CI: 0·12–0·72) approximately a 0·8-point improvement... [ABSTRACT FROM AUTHOR]