Purpose To investigate the outcome of manuscripts submitted to the American Journal of Ophthalmology (AJO) between July 23, 2002 and December 31, 2003. Design Observational series. Methods Data were collected on all Full-Length Articles and Brief Reports submitted to the AJO. Data were recorded for rejected or withdrawn manuscripts about the date of submission and decision, category of decision, type of article, manuscript region of origin, alternate journal of manuscript, date of publication, and impact factor and immediacy index of the subsequent journal. Corresponding data were collected from the manuscripts accepted over the same period. The Advanced PubMed online database was searched to determine if the rejected or withdrawn manuscripts were published elsewhere. The impact factor and the immediacy index of the journal of the subsequent journal was then recorded and compared with those of the AJO, using the year 2004 for comparison. Results Of 2,026 manuscripts submitted, 1,444 were rejected by the AJO or withdrawn by the authors and 50% of these were subsequently published elsewhere in a PubMed listed journal. The rejected or withdrawn articles were typically published in lower impact journals, most commonly in general ophthalmology journals in the author’s region or in subspecialty journals, although several were published in higher impact journals. The 727 articles were published in 94 different journals and usually with an extended delay. Conclusions Rejection of a manuscript by the AJO does not preclude publication, but rejected manuscripts are published more often in journals that serve a smaller readership and are cited less frequently, although exceptions exist.