BACKGROUND: The Immune defence trial documented short term impacts on RTIs for nasal sprays, and a stress-management and physical activity website. AIM: To estimate the impact of sprays and the website after 12 months. DESIGN: Four arm parallel randomised controlled trial Setting. Participants with co-morbidities and/or >=3 self-reported recurrent illnesses recruited by mailed invitation. Methods Participants were randomised by online software (stratified by recurrent illness and comorbidities) to i) usual care (n=3451) ii) Vick's First-Defence (VFD) spray (n=3448) (2 sprays/nostril, <=6x/day) iii) isotonic saline spray (n=3450) (same dosing) or iv) a website promoting physical activity and stress-management (n=3450). PRIMARY OUTCOME: respiratory illness days. FINDINGS: Usual care participants (n=3051) had on average 22 illness days, reduced by VFD ((n=3076; 18 days, adjusted incidence rate ratio (IRR) 0.84, 99% CIs 0.79,0.90; p<0.0001), and saline (n=3142; 18 days, IRR 0.83; 0.78,0.89; p<0.0001), but not the website (n=2811; 20 days, IRR 0.94;0.88,1.01, p=0.03)). The website reduced incident infections (0.96,0.93 to 0.99, p=0.006). All interventions reduced symptom severity and work-days lost, both spray groups reported lower intention to consult and fewer falls, and there were fewer antibiotic courses and practice visits with saline. Among those with recurrent illness saline had the most impact on both recurrence and symptom days (respectively 0.93 (0.87,0.99), 0.70 (0.60,0.82)). Headache were higher for VFD and lower for saline (7.8%, 3.4% respectively; 4.7% usual care). CONCLUSION: Widely available, inexpensive sprays and a website promoting self-care reduce the incidence, duration and/ or severity of RTIs and impact work-days lost and healthcare use.