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The study examines publication output among professional librarians in four public universities in Ghana. The major objectives of the study were to determine publication output of the professional librarians and investigate the challenges confronting publication efforts of the professional librarians, among others. The mixed methods approach was employed for the study. The questionnaire was used to collect data from 47 professional librarians and four university librarians were also interviewed. The Statistical Package for Social Sciences (SPSS) software was used to analyse the quantitative data collected through the questionnaire, while content analysis was employed to analyse the qualitative data that was gathered from the interviews. The analysis used was descriptive statistics, comprising frequencies, percentages and means, among others. The major findings revealed that publication output was low among the respondents and journal articles were the most popular publication format. Another finding also indicated that the higher ranked professional librarians were more prolific than lower ranked ones, while the professional librarians from two of the public universities were most prolific. Generally, the results could not establish correlation between working experience and publication output of the professional librarians. The results revealed that challenges that hampered publication efforts of the professional librarians were lack of time and heavy workload, inflexible work schedule, and absence of formal mentoring programme. It is recommended that the professional librarians should be provided with work time for research and publication, training, workshops and seminars, formal mentoring programmes, and collaboration, among others, to facilitate their research and scholarly publication efforts.