OBJECTIVE: Total hip replacement (THR) and total knee replacement (TKR) (arthroplasty) surgery for end-stage osteoarthritis (OA) are ideal candidates for optimization through an algorithmic care pathway. Using a comparative effectiveness study design, we compared the effectiveness of a new clinical pathway (NCP) featuring central intake clinics, dedicated inpatient resources, care guidelines and efficiency benchmarks vs the standard of care (SOC) for THR or TKR. METHODS: We compared patients undergoing primary THR and TKR who received surgery in NCP vs SOC in a randomised controlled trial within the trial timeframe. 1,570 patients (1,066 SOC and 504 NCP patients) that underwent surgery within the study timeframe from urban and rural practice settings were included. The primary endpoint was improvement in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) overall score over 12months post-surgery. Secondary endpoints were improvements in the Physical Function (PF) and Bodily Pain (BP) domains of the Short Form 36 (SF-36). RESULTS: NCP patients had significantly greater improvements from baseline WOMAC scores compared to SOC patients after adjusting for covariates (treatment effect=2.56; 95% confidence interval (CI) [1.10-4.01]). SF-36 BP scores were significantly improved for both hip and knee patients in the NCP (treatment effect=3.01, 95% CI [0.70-5.32]), but SF-36 PF scores were not. Effects of the NCP were more pronounced in knee patients. CONCLUSION: While effect sizes were small compared with major effects of the surgery itself, an evidence-informed clinical pathway can improve health related quality of life (HRQoL) of hip and knee arthroplasty patients with degenerative joint disorder in routine clinical practice for up to 12months post-operatively. CLINICALTRIALS.GOV IDENTIFIER: NCT00277186.