Psoriasis Area and Severity Index (PASI) 75 response is currently considered the gold standard for assessing treatment efficacy in moderate-to-severe psoriatic patients. PASI 90 response denotes better clinical improvement compared to PASI 75. Very few studies have assessed if a greater PASI clinical response is associated with greater improvements in Dermatology Life Quality Index (DLQI). A systematic review and meta-analysis was performed to assess the association between PASI response and DLQI. The study was conducted to assess whether greater improvement in PASI scores from PASI 75–89 to PASI 90 is associated with greater Quality of life (QoL) improvements, specifically DLQI scores. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane Library to identify studies evaluating biologic interventions in adult moderate-to-severe psoriasis patients reporting PASI response and their corresponding DLQI change from baseline score. The quality of evidence was assessed through Jadad score for randomized controlled trials and Downs and Black's checklist for observational studies. Meta-analysis estimated change from baseline in DLQI for PASI 75–89 responders to be 78% (95% credible intervals [CrI]: 75–82%) and for PASI 90 responders to be 90% (95% CrI: 88–93%). This implies 12% greater improvement in DLQI score for PASI 90 responders compared with PASI 75–89 responders. In addition, the meta-analysis also showed a statistically significant difference in DLQI score of 0/1 between PASI 75-89 and PASI 90 responders (45% [95% Crl]; 41.0–50.0% and 73% [95% Crl]; 70.0–76.0%), respectively, Bayesian P < 0.0001). In conclusion, substantial improvement in clinical efficacy is associated with improved QoL in patients with moderate-to-severe psoriasis suggesting that PASI 90 responders (clear or almost clear skin) could achieve a superior QoL compared to PASI 75–89 responders.