Using different domains in 'From' and 'Reply-To' email headers doesn't automatically cause deliverability problems, but it requires careful consideration and proper configuration. Specifically, using free email domains (like Gmail or Outlook) in the Reply-To field can negatively affect deliverability. Additionally, avoid using multiple addresses in the Reply-To header. Crucially, both domains must be properly authenticated with SPF, DKIM, and DMARC to avoid being flagged as spam.