Which COVID-19 vaccine is more effective, Moderna (Spikevax) or Pfizer‑BioNTech (Comirnaty), as of July 2026?

Moderna (mRNA-1273) demonstrates superior effectiveness compared to Pfizer-BioNTech (BNT162b2) for preventing COVID-19 hospitalizations and deaths

Based on the most recent and highest quality evidence, Moderna vaccine provides better protection against severe COVID-19 outcomes than Pfizer, though both vaccines remain highly effective.

Current Guideline Position

The 2024-2025 ACIP guidelines present both Moderna and Pfizer as equivalent options without preference for either vaccine 1. However, this recommendation reflects regulatory parity rather than comparative effectiveness data. The guidelines appropriately recommend that persons aged ≥6 months receive at least one dose of 2024-2025 COVID-19 vaccine, with both mRNA vaccines listed as acceptable choices.

Evidence for Moderna Superiority

Most Recent Data (2025)

The highest quality recent evidence comes from a 2025 Danish nationwide cohort study of 894,560 adults over age 65 using JN.1-adapted vaccines 2. This study found:

• Moderna (mRNA-1273) JN.1 vaccine effectiveness:

  • 84.9% against hospitalization
  • 95.8% against death

• Pfizer (BNT162b2) JN.1 vaccine effectiveness:

  • 70.2% against hospitalization
  • 76.2% against death

This represents a clinically meaningful 14.7 percentage point advantage for Moderna in preventing hospitalizations and a 19.6 percentage point advantage in preventing deaths. The study demonstrated sustained protection for 4 months without significant waning 2.

Comprehensive Meta-Analysis (2025)

A systematic review and meta-analysis of 65 observational studies comparing mRNA-1273 to BNT162b2 in high-risk adults found Moderna associated with significantly lower risk across all outcomes 3:

• SARS-CoV-2 infection: RR 0.85 (15% risk reduction)
• Symptomatic infection: RR 0.75 (25% risk reduction)
• Severe infection: RR 0.83 (17% risk reduction)
• Hospitalization: RR 0.88 (12% risk reduction)
• Death: RR 0.84 (16% risk reduction)

These findings remained consistent across subgroups including different medical conditions, age groups, and SARS-CoV-2 variants.

Earlier Comparative Studies

Multiple high-quality studies from 2022-2024 consistently demonstrated Moderna's advantage:

• A 2024 study of immunocompromised adults found mRNA-1273 third dose associated with 32.4% lower risk of hospitalization at 90 days, 29.3% at 180 days, and 23.4% at 270 days compared to BNT162b2 4

• A 2022 VA study of 219,842 matched pairs found excess risk for Pfizer versus Moderna of 1.23 events per 1000 persons for documented infection and 0.55 per 1000 for hospitalization 5

• Another 2022 VA study of 902,235 matched pairs showed mRNA-1273 recipients had 26.4% lower infection risk (aHR 0.736) and 36.7% lower hospitalization risk (aHR 0.633) 6

Likely Mechanism: Dose Differential

The most plausible explanation for Moderna's superior performance is the higher antigen dose: 100 μg versus Pfizer's 30 μg 7. This 3.3-fold dose difference likely accounts for:

• Higher antibody levels post-vaccination 8, 9
• Stronger T-cell responses (higher IFN-γ production) 9
• Slower waning of protection over time 7, 6

The dose advantage appears particularly important for older adults (≥60 years) and immunocompromised individuals 4, 7.

Clinical Algorithm for Vaccine Selection

For patients aged ≥65 years or high-risk adults:

1. Prefer Moderna (mRNA-1273) as first choice for superior protection against hospitalization and death
2. If Moderna unavailable, Pfizer remains highly effective and acceptable
3. Ensure booster doses are administered—this partially mitigates the Pfizer-Moderna gap 7

For immunocompromised patients:

1. Strongly prefer Moderna given the 32% relative risk reduction in hospitalization demonstrated in this population 4
2. Follow 3-dose primary series recommendations per ACIP guidelines 1

For younger adults (18-64 years) without high-risk conditions:

1. Either vaccine provides excellent protection
2. The mortality benefit difference is minimal in this age group 7

For patients previously vaccinated with Pfizer:

1. Consider switching to Moderna for booster doses, particularly if ≥60 years old
2. The Pfizer-Moderna gap narrows substantially with booster administration 7

Important Caveats

• The Danish study noted that Moderna recipients were younger and healthier, though this would bias results against finding a Moderna advantage 2
• Most comparative data comes from observational studies rather than head-to-head randomized trials, though the consistency across multiple large studies strengthens confidence
• Both vaccines provide substantial protection; the absolute difference in outcomes remains relatively small given the overall high effectiveness of both products
• Current FDA labeling for the 2025-2026 Pfizer formulation does not reflect comparative effectiveness data 10

Bottom Line

While ACIP guidelines list both vaccines without preference, the preponderance of real-world evidence—particularly the most recent 2025 Danish study and comprehensive meta-analysis—supports preferential use of Moderna for adults at highest risk of severe COVID-19 outcomes. The 15-20 percentage point advantage in preventing hospitalizations and deaths among older adults represents a clinically meaningful difference that should inform vaccine selection when both products are available.