Background: To evaluate if early improvements in pain and function with subcutaneous tanezumab are meaningful and sustained over 24 weeks. Methods: Patients with moderate-to-severe osteoarthritis (hip or knee) in Europe and Japan were randomized to placebo, tanezumab 2.5 mg or tanezumab 5 mg (baseline, Week 8 and Week 16). Outcomes included: average daily index joint pain score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales, rescue medication use, WOMAC responders (within-patient ≥30% reduction in WOMAC Pain or Physical Function), Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders (within-patient) and Patient-reported Treatment Impact Assessment-Modified questionnaire. Results: Patients received placebo (n = 282), tanezumab 2.5 mg (n = 283) or tanezumab 5 mg (n = 284). Changes from baseline in average daily index joint pain (within the first week) and WOMAC subscales (Week 2 through Week 24) were greater for each tanezumab group versus placebo (least squares [LS] mean, unadjusted p ≤ .05). Rescue medication use (days/week) was lower for each tanezumab group versus placebo from Week 2 through Week 12 (LS mean, unadjusted p ≤ .05) but not at Week 16 or 24. A higher proportion of each tanezumab group than placebo achieved ≥30% reduction from baseline in WOMAC Pain or Physical Function, or OMERACT-OARSI response (Week 2 through Week 24, unadjusted p ≤ .05), or were satisfied with treatment at Week 24 (unadjusted p ≤ .05). Conclusions: Subcutaneous tanezumab, compared with placebo, reduced pain within the first week, and pain and function were improved throughout 24 weeks. The proportions of responders and patients satisfied were higher with tanezumab than placebo. ClinicalTrials.gov:NCT02709486. Significance: This exploratory analysis of data from a placebo-controlled, Phase 3 study of patients with moderate-to-severe osteoarthritis of the hip or knee for whom standard analgesics were not effective or could not be taken, found that onset of efficacy of subcutaneous tanezumab was within the first week, and efficacy was maintained through the 24-week treatment period. Tanezumab was effective in those patients with the most radiologically severe osteoarthritis.