<p class="abstract"><strong>Background:</strong> The objective of the study was to assess the pattern of needle stick and sharp injuries and associated factors among healthcare workers in Gambella Town, Southwest Ethiopia.</p><p class="abstract"><strong>Methods:</strong> Institutional-based cross-sectional study was conducted from 05 March to 20 April 2019. A total of 368 healthcare workers were recruited using a systematic random sampling procedure. The data were entered into Epi info 7 and exported to statistical package for the social sciences (SPSS) version 21 for analysis. P≤0.20 was used to select variables from bivariable logistic analysis to multivariable logistic analysis. P value of ≤0.05 with 95% confidence level was used to identify variables that were associated with needle stick and sharp injuries. </p><p class="abstract"><strong>Results:</strong> The prevalence of needle stick and sharp injuries among healthcare workers in Gambella town was 113 (32.2%) 95% CI (27.43, 36.97) with mean age of 30.35±7.73. Work experience >10 years [AOR=2.24, 95% CI: (1.13, 4.43)], absence of training on occupational health and safety [AOR=4.89, 95% CI: (2.21, 10.84)], working more than 48 hours/week [AOR=3.44, 95% CI: (1.76, 6.74)], dissatisfaction with their work [AOR=3.76, 95% CI: (2.12, 6.69)], having low risk perception [AOR=5.82, 95% CI: (2.59, 13.07)], and having moderate risk perception [AOR=3.44, 95% CI: (1.83, 6.49)] were significantly associated with needle stick and sharp injuries.</p><p class="abstract"><strong>Conclusions:</strong> There was high prevalence of needle stick and sharp injuries among healthcare workers in Gambella town. Lack of training, low-risk perception, dissatisfaction with the working environment, long working hours, and long working experience were associated with needle stick and sharp injuries.</p>